Maternal HIV Infection and Placental Malaria Reduce Transplacental Antibody Transfer and Tetanus Antibody Levels in Newborns in Kenya
Identifieur interne : 002C68 ( Istex/Corpus ); précédent : 002C67; suivant : 002C69Maternal HIV Infection and Placental Malaria Reduce Transplacental Antibody Transfer and Tetanus Antibody Levels in Newborns in Kenya
Auteurs : Phillippa Cumberland ; Caroline E. Shulman ; P. A. Chris Maple ; Judith N. Bulmer ; Edgar K. Dorman ; Ken Kawuondo ; Kevin Marsh ; Felicity T. CuttsSource :
- The Journal of Infectious Diseases [ 0022-1899 ] ; 2007-08-15.
Abstract
Background. In clinical trials, maternal tetanus toxoid (TT) vaccination is effective in protecting newborns against tetanus infection, but inadequate placental transfer of tetanus antibodies may contribute to lower-thanexpected rates of protection in routine practice. We studied the effect of placental malaria and maternal human immunodeficiency virus (HIV) infection on placental transfer of antibodies to tetanus. Methods. A total of 704 maternal-cord paired serum samples were tested by ELISA for antibodies to tetanus. The HIV status of all women was determined by an immunoglobulin G antibody-capture particle-adherence test, and placental malaria was determined by placental biopsy. Maternal history of TT vaccination was recorded. Results. Tetanus antibody levels were reduced by 52% (95% confidence interval [CI], 30%–67%) in newborns of HIV-infected women and by 48% (95% CI, 26%–62%) in newborns whose mothers had active-chronic or past placental malaria. Thirty-seven mothers (5.3%) and 55 newborns (7.8%) had tetanus antibody levels <0.1 IU/mL (i.e., were seronegative). Mothers' self-reported history of lack of tetanus immunization was the strongest predictor of seronegativity and of tetanus antibody levels in maternal and cord serum. Conclusion. Malarial and HIV infections may hinder efforts to eliminate maternal and neonatal tetanus, making implementation of the current policy for mass vaccination of women of childbearing age an urgent priority.
Url:
DOI: 10.1086/519845
Links to Exploration step
ISTEX:88C118EFCA60DB4F8740D8E73E965AF1B408762CLe document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title>Maternal HIV Infection and Placental Malaria Reduce Transplacental Antibody Transfer and Tetanus Antibody Levels in Newborns in Kenya</title><author><name sortKey="Cumberland, Phillippa" sort="Cumberland, Phillippa" uniqKey="Cumberland P" first="Phillippa" last="Cumberland">Phillippa Cumberland</name><affiliation><mods:affiliation>Centre for Paediatric Epidemiology and Biostatistics, Institute of Child Health, London</mods:affiliation></affiliation></author><author><name sortKey="Shulman, Caroline E" sort="Shulman, Caroline E" uniqKey="Shulman C" first="Caroline E." last="Shulman">Caroline E. Shulman</name><affiliation><mods:affiliation>Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London</mods:affiliation></affiliation><affiliation><mods:affiliation>Kenya Medical Research Institute, Centre for Geographical Medicine Research-Coast, Kilifi, Kenya</mods:affiliation></affiliation></author><author><name sortKey="Chris Maple, P A" sort="Chris Maple, P A" uniqKey="Chris Maple P" first="P. A." last="Chris Maple">P. A. Chris Maple</name><affiliation><mods:affiliation>Virus Reference Department, Health Protection Agency Centre for Infections, London</mods:affiliation></affiliation></author><author><name sortKey="Bulmer, Judith N" sort="Bulmer, Judith N" uniqKey="Bulmer J" first="Judith N." last="Bulmer">Judith N. Bulmer</name><affiliation><mods:affiliation>School of Clinical and Laboratory Sciences (Pathology), Newcastle University, Newcastle upon Tyne, United Kingdom</mods:affiliation></affiliation></author><author><name sortKey="Dorman, Edgar K" sort="Dorman, Edgar K" uniqKey="Dorman E" first="Edgar K." last="Dorman">Edgar K. Dorman</name><affiliation><mods:affiliation>Homerton University Hospital NHS Foundation Trust, London</mods:affiliation></affiliation><affiliation><mods:affiliation>Kenya Medical Research Institute, Centre for Geographical Medicine Research-Coast, Kilifi, Kenya</mods:affiliation></affiliation></author><author><name sortKey="Kawuondo, Ken" sort="Kawuondo, Ken" uniqKey="Kawuondo K" first="Ken" last="Kawuondo">Ken Kawuondo</name><affiliation><mods:affiliation>Kenya Medical Research Institute, Centre for Geographical Medicine Research-Coast, Kilifi, Kenya</mods:affiliation></affiliation></author><author><name sortKey="Marsh, Kevin" sort="Marsh, Kevin" uniqKey="Marsh K" first="Kevin" last="Marsh">Kevin Marsh</name><affiliation><mods:affiliation>Kenya Medical Research Institute, Centre for Geographical Medicine Research-Coast, Kilifi, Kenya</mods:affiliation></affiliation></author><author><name sortKey="Cutts, Felicity T" sort="Cutts, Felicity T" uniqKey="Cutts F" first="Felicity T." last="Cutts">Felicity T. Cutts</name><affiliation><mods:affiliation>Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: felicity.cutts@lshtm.ac.uk</mods:affiliation></affiliation><affiliation><mods:affiliation>Reprints or correspondence: Felicity Cutts London School of Hygiene and Tropical Medicine Keppel St. London WC1 7HT UK</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: felicity.cutts@lshtm.ac.uk</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:88C118EFCA60DB4F8740D8E73E965AF1B408762C</idno><date when="2007" year="2007">2007</date><idno type="doi">10.1086/519845</idno><idno type="url">https://api.istex.fr/document/88C118EFCA60DB4F8740D8E73E965AF1B408762C/fulltext/pdf</idno><idno type="wicri:Area/Istex/Corpus">002C68</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">002C68</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a">Maternal HIV Infection and Placental Malaria Reduce Transplacental Antibody Transfer and Tetanus Antibody Levels in Newborns in Kenya</title><author><name sortKey="Cumberland, Phillippa" sort="Cumberland, Phillippa" uniqKey="Cumberland P" first="Phillippa" last="Cumberland">Phillippa Cumberland</name><affiliation><mods:affiliation>Centre for Paediatric Epidemiology and Biostatistics, Institute of Child Health, London</mods:affiliation></affiliation></author><author><name sortKey="Shulman, Caroline E" sort="Shulman, Caroline E" uniqKey="Shulman C" first="Caroline E." last="Shulman">Caroline E. Shulman</name><affiliation><mods:affiliation>Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London</mods:affiliation></affiliation><affiliation><mods:affiliation>Kenya Medical Research Institute, Centre for Geographical Medicine Research-Coast, Kilifi, Kenya</mods:affiliation></affiliation></author><author><name sortKey="Chris Maple, P A" sort="Chris Maple, P A" uniqKey="Chris Maple P" first="P. A." last="Chris Maple">P. A. Chris Maple</name><affiliation><mods:affiliation>Virus Reference Department, Health Protection Agency Centre for Infections, London</mods:affiliation></affiliation></author><author><name sortKey="Bulmer, Judith N" sort="Bulmer, Judith N" uniqKey="Bulmer J" first="Judith N." last="Bulmer">Judith N. Bulmer</name><affiliation><mods:affiliation>School of Clinical and Laboratory Sciences (Pathology), Newcastle University, Newcastle upon Tyne, United Kingdom</mods:affiliation></affiliation></author><author><name sortKey="Dorman, Edgar K" sort="Dorman, Edgar K" uniqKey="Dorman E" first="Edgar K." last="Dorman">Edgar K. Dorman</name><affiliation><mods:affiliation>Homerton University Hospital NHS Foundation Trust, London</mods:affiliation></affiliation><affiliation><mods:affiliation>Kenya Medical Research Institute, Centre for Geographical Medicine Research-Coast, Kilifi, Kenya</mods:affiliation></affiliation></author><author><name sortKey="Kawuondo, Ken" sort="Kawuondo, Ken" uniqKey="Kawuondo K" first="Ken" last="Kawuondo">Ken Kawuondo</name><affiliation><mods:affiliation>Kenya Medical Research Institute, Centre for Geographical Medicine Research-Coast, Kilifi, Kenya</mods:affiliation></affiliation></author><author><name sortKey="Marsh, Kevin" sort="Marsh, Kevin" uniqKey="Marsh K" first="Kevin" last="Marsh">Kevin Marsh</name><affiliation><mods:affiliation>Kenya Medical Research Institute, Centre for Geographical Medicine Research-Coast, Kilifi, Kenya</mods:affiliation></affiliation></author><author><name sortKey="Cutts, Felicity T" sort="Cutts, Felicity T" uniqKey="Cutts F" first="Felicity T." last="Cutts">Felicity T. Cutts</name><affiliation><mods:affiliation>Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: felicity.cutts@lshtm.ac.uk</mods:affiliation></affiliation><affiliation><mods:affiliation>Reprints or correspondence: Felicity Cutts London School of Hygiene and Tropical Medicine Keppel St. London WC1 7HT UK</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: felicity.cutts@lshtm.ac.uk</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="2007-08-15">2007-08-15</date><biblScope unit="volume">196</biblScope><biblScope unit="issue">4</biblScope><biblScope unit="page" from="550">550</biblScope><biblScope unit="page" to="557">557</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. In clinical trials, maternal tetanus toxoid (TT) vaccination is effective in protecting newborns against tetanus infection, but inadequate placental transfer of tetanus antibodies may contribute to lower-thanexpected rates of protection in routine practice. We studied the effect of placental malaria and maternal human immunodeficiency virus (HIV) infection on placental transfer of antibodies to tetanus. Methods. A total of 704 maternal-cord paired serum samples were tested by ELISA for antibodies to tetanus. The HIV status of all women was determined by an immunoglobulin G antibody-capture particle-adherence test, and placental malaria was determined by placental biopsy. Maternal history of TT vaccination was recorded. Results. Tetanus antibody levels were reduced by 52% (95% confidence interval [CI], 30%–67%) in newborns of HIV-infected women and by 48% (95% CI, 26%–62%) in newborns whose mothers had active-chronic or past placental malaria. Thirty-seven mothers (5.3%) and 55 newborns (7.8%) had tetanus antibody levels <0.1 IU/mL (i.e., were seronegative). Mothers' self-reported history of lack of tetanus immunization was the strongest predictor of seronegativity and of tetanus antibody levels in maternal and cord serum. Conclusion. Malarial and HIV infections may hinder efforts to eliminate maternal and neonatal tetanus, making implementation of the current policy for mass vaccination of women of childbearing age an urgent priority.</div></front></TEI><istex><corpusName>oup</corpusName><author><json:item><name>Phillippa Cumberland</name><affiliations><json:string>Centre for Paediatric Epidemiology and Biostatistics, Institute of Child Health, London</json:string></affiliations></json:item><json:item><name>Caroline E. Shulman</name><affiliations><json:string>Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London</json:string><json:string>Kenya Medical Research Institute, Centre for Geographical Medicine Research-Coast, Kilifi, Kenya</json:string></affiliations></json:item><json:item><name>P. A. Chris Maple</name><affiliations><json:string>Virus Reference Department, Health Protection Agency Centre for Infections, London</json:string></affiliations></json:item><json:item><name>Judith N. Bulmer</name><affiliations><json:string>School of Clinical and Laboratory Sciences (Pathology), Newcastle University, Newcastle upon Tyne, United Kingdom</json:string></affiliations></json:item><json:item><name>Edgar K. Dorman</name><affiliations><json:string>Homerton University Hospital NHS Foundation Trust, London</json:string><json:string>Kenya Medical Research Institute, Centre for Geographical Medicine Research-Coast, Kilifi, Kenya</json:string></affiliations></json:item><json:item><name>Ken Kawuondo</name><affiliations><json:string>Kenya Medical Research Institute, Centre for Geographical Medicine Research-Coast, Kilifi, Kenya</json:string></affiliations></json:item><json:item><name>Kevin Marsh</name><affiliations><json:string>Kenya Medical Research Institute, Centre for Geographical Medicine Research-Coast, Kilifi, Kenya</json:string></affiliations></json:item><json:item><name>Felicity T. Cutts</name><affiliations><json:string>Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London</json:string><json:string>E-mail: felicity.cutts@lshtm.ac.uk</json:string></affiliations></json:item></author><language><json:string>unknown</json:string></language><originalGenre><json:string>research-article</json:string></originalGenre><abstract>Background. In clinical trials, maternal tetanus toxoid (TT) vaccination is effective in protecting newborns against tetanus infection, but inadequate placental transfer of tetanus antibodies may contribute to lower-thanexpected rates of protection in routine practice. We studied the effect of placental malaria and maternal human immunodeficiency virus (HIV) infection on placental transfer of antibodies to tetanus. Methods. A total of 704 maternal-cord paired serum samples were tested by ELISA for antibodies to tetanus. The HIV status of all women was determined by an immunoglobulin G antibody-capture particle-adherence test, and placental malaria was determined by placental biopsy. Maternal history of TT vaccination was recorded. Results. Tetanus antibody levels were reduced by 52% (95% confidence interval [CI], 30%–67%) in newborns of HIV-infected women and by 48% (95% CI, 26%–62%) in newborns whose mothers had active-chronic or past placental malaria. Thirty-seven mothers (5.3%) and 55 newborns (7.8%) had tetanus antibody levels >0.1 IU/mL (i.e., were seronegative). Mothers' self-reported history of lack of tetanus immunization was the strongest predictor of seronegativity and of tetanus antibody levels in maternal and cord serum. Conclusion. Malarial and HIV infections may hinder efforts to eliminate maternal and neonatal tetanus, making implementation of the current policy for mass vaccination of women of childbearing age an urgent priority.</abstract><qualityIndicators><score>9.375</score><pdfWordCount>4891</pdfWordCount><pdfCharCount>32178</pdfCharCount><pdfVersion>1.2</pdfVersion><pdfPageCount>8</pdfPageCount><pdfPageSize>612 x 792 pts (letter)</pdfPageSize><refBibsNative>true</refBibsNative><abstractWordCount>207</abstractWordCount><abstractCharCount>1470</abstractCharCount><keywordCount>0</keywordCount></qualityIndicators><title>Maternal HIV Infection and Placental Malaria Reduce Transplacental Antibody Transfer and Tetanus Antibody Levels in Newborns in Kenya</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>4</issue><pages><first>550</first><last>557</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>10.1086/519845</json:string></doi><id>88C118EFCA60DB4F8740D8E73E965AF1B408762C</id><score>1</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/document/88C118EFCA60DB4F8740D8E73E965AF1B408762C/fulltext/pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/document/88C118EFCA60DB4F8740D8E73E965AF1B408762C/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/88C118EFCA60DB4F8740D8E73E965AF1B408762C/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a">Maternal HIV Infection and Placental Malaria Reduce Transplacental Antibody Transfer and Tetanus Antibody Levels in Newborns in Kenya</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">Maternal HIV Infection and Placental Malaria Reduce Transplacental Antibody Transfer and Tetanus Antibody Levels in Newborns in Kenya</title><author xml:id="author-0000"><persName><forename type="first">Phillippa</forename><surname>Cumberland</surname></persName><affiliation>Centre for Paediatric Epidemiology and Biostatistics, Institute of Child Health, London</affiliation></author><author xml:id="author-0001"><persName><forename type="first">Caroline E.</forename><surname>Shulman</surname></persName><affiliation>Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London</affiliation><affiliation>Kenya Medical Research Institute, Centre for Geographical Medicine Research-Coast, Kilifi, Kenya</affiliation></author><author xml:id="author-0002"><persName><forename type="first">P. A.</forename><surname>Chris Maple</surname></persName><affiliation>Virus Reference Department, Health Protection Agency Centre for Infections, London</affiliation></author><author xml:id="author-0003"><persName><forename type="first">Judith N.</forename><surname>Bulmer</surname></persName><affiliation>School of Clinical and Laboratory Sciences (Pathology), Newcastle University, Newcastle upon Tyne, United Kingdom</affiliation></author><author xml:id="author-0004"><persName><forename type="first">Edgar K.</forename><surname>Dorman</surname></persName><affiliation>Homerton University Hospital NHS Foundation Trust, London</affiliation><affiliation>Kenya Medical Research Institute, Centre for Geographical Medicine Research-Coast, Kilifi, Kenya</affiliation></author><author xml:id="author-0005"><persName><forename type="first">Ken</forename><surname>Kawuondo</surname></persName><affiliation>Kenya Medical Research Institute, Centre for Geographical Medicine Research-Coast, Kilifi, Kenya</affiliation></author><author xml:id="author-0006"><persName><forename type="first">Kevin</forename><surname>Marsh</surname></persName><affiliation>Kenya Medical Research Institute, Centre for Geographical Medicine Research-Coast, Kilifi, Kenya</affiliation></author><author xml:id="author-0007" corresp="yes"><persName><forename type="first">Felicity T.</forename><surname>Cutts</surname></persName><email>felicity.cutts@lshtm.ac.uk</email><email>felicity.cutts@lshtm.ac.uk</email><affiliation>Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London</affiliation><affiliation>Reprints or correspondence: Felicity Cutts London School of Hygiene and Tropical Medicine Keppel St. London WC1 7HT UK</affiliation></author><idno type="istex">88C118EFCA60DB4F8740D8E73E965AF1B408762C</idno><idno type="ark">ark:/67375/HXZ-JWM9PXFM-5</idno><idno type="DOI">10.1086/519845</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="2007-08-15"></date><biblScope unit="volume">196</biblScope><biblScope unit="issue">4</biblScope><biblScope unit="page" from="550">550</biblScope><biblScope unit="page" to="557">557</biblScope></imprint></monogr></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2007</date></creation><abstract><p>Background. In clinical trials, maternal tetanus toxoid (TT) vaccination is effective in protecting newborns against tetanus infection, but inadequate placental transfer of tetanus antibodies may contribute to lower-thanexpected rates of protection in routine practice. We studied the effect of placental malaria and maternal human immunodeficiency virus (HIV) infection on placental transfer of antibodies to tetanus. Methods. A total of 704 maternal-cord paired serum samples were tested by ELISA for antibodies to tetanus. The HIV status of all women was determined by an immunoglobulin G antibody-capture particle-adherence test, and placental malaria was determined by placental biopsy. Maternal history of TT vaccination was recorded. Results. Tetanus antibody levels were reduced by 52% (95% confidence interval [CI], 30%–67%) in newborns of HIV-infected women and by 48% (95% CI, 26%–62%) in newborns whose mothers had active-chronic or past placental malaria. Thirty-seven mothers (5.3%) and 55 newborns (7.8%) had tetanus antibody levels <0.1 IU/mL (i.e., were seronegative). Mothers' self-reported history of lack of tetanus immunization was the strongest predictor of seronegativity and of tetanus antibody levels in maternal and cord serum. Conclusion. Malarial and HIV infections may hinder efforts to eliminate maternal and neonatal tetanus, making implementation of the current policy for mass vaccination of women of childbearing age an urgent priority.</p></abstract><textClass><keywords scheme="Journal Subject"><list><head></head><item><term>HIV/AIDS</term></item></list></keywords></textClass><textClass><keywords scheme="Journal Subject"><list><head></head><item><term>Major Article</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2007-08-15">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/document/88C118EFCA60DB4F8740D8E73E965AF1B408762C/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">10.1086/519845</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Major Articles and Brief Reports</subject>
<subj-group>
<subject>HIV/AIDS</subject>
<subj-group>
<subject>Major Article</subject>
</subj-group>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>Maternal HIV Infection and Placental Malaria Reduce Transplacental Antibody Transfer and Tetanus Antibody Levels in Newborns in Kenya</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Cumberland</surname>
<given-names>Phillippa</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Shulman</surname>
<given-names>Caroline E.</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
<xref ref-type="aff" rid="A6">6</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Chris Maple</surname>
<given-names>P. A.</given-names>
</name>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Bulmer</surname>
<given-names>Judith N.</given-names>
</name>
<xref ref-type="aff" rid="A5">5</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Dorman</surname>
<given-names>Edgar K.</given-names>
</name>
<xref ref-type="aff" rid="A4">4</xref>
<xref ref-type="aff" rid="A6">6</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Kawuondo</surname>
<given-names>Ken</given-names></name>
<xref ref-type="aff" rid="A6">6</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Marsh</surname>
<given-names>Kevin</given-names>
</name>
<xref ref-type="aff" rid="A6">6</xref>
</contrib>
<contrib contrib-type="author" corresp="yes">
<name>
<surname>Cutts</surname>
<given-names>Felicity T.</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
<xref ref-type="corresp" rid="cor1"></xref>
</contrib>
<aff id="A1">
<label>1</label>
<institution>Centre for Paediatric Epidemiology and Biostatistics, Institute of Child Health</institution>, <addr-line>London</addr-line>
</aff>
<aff id="A2">
<label>2</label>
<institution>Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine</institution>, <addr-line>London</addr-line>
</aff>
<aff id="A3">
<label>3</label>
<institution>Virus Reference Department, Health Protection Agency Centre for Infections</institution>, <addr-line>London</addr-line>
</aff>
<aff id="A4">
<label>4</label>
<institution>Homerton University Hospital NHS Foundation Trust</institution>, <addr-line>London</addr-line>
</aff>
<aff id="A5">
<label>5</label>
<institution>School of Clinical and Laboratory Sciences (Pathology), Newcastle University</institution>, <addr-line>Newcastle upon Tyne, United Kingdom</addr-line>
</aff>
<aff id="A6">
<label>6</label>
<institution>Kenya Medical Research Institute, Centre for Geographical Medicine Research-Coast</institution>, <addr-line>Kilifi, Kenya</addr-line>
</aff>
</contrib-group>
<author-notes>
<corresp id="cor1">Reprints or correspondence: Felicity Cutts London School of Hygiene and Tropical Medicine Keppel St. London WC1 7HT UK (<email>felicity.cutts@lshtm.ac.uk</email>).</corresp>
</author-notes>
<pub-date pub-type="ppub">
<day>15</day>
<month>8</month>
<year>2007</year>
</pub-date>
<volume>196</volume>
<issue>4</issue>
<fpage>550</fpage>
<lpage>557</lpage>
<history>
<date date-type="received">
<day>13</day>
<month>12</month>
<year>2006</year>
</date>
<date date-type="accepted">
<day>8</day>
<month>2</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> In clinical trials, maternal tetanus toxoid (TT) vaccination is effective in protecting newborns against tetanus infection, but inadequate placental transfer of tetanus antibodies may contribute to lower-thanexpected rates of protection in routine practice. We studied the effect of placental malaria and maternal human immunodeficiency virus (HIV) infection on placental transfer of antibodies to tetanus.</p>
<p><bold><italic>Methods.</italic></bold> A total of 704 maternal-cord paired serum samples were tested by ELISA for antibodies to tetanus. The HIV status of all women was determined by an immunoglobulin G antibody-capture particle-adherence test, and placental malaria was determined by placental biopsy. Maternal history of TT vaccination was recorded.</p>
<p><bold><italic>Results.</italic></bold> Tetanus antibody levels were reduced by 52% (95% confidence interval [CI], 30%–67%) in newborns of HIV-infected women and by 48% (95% CI, 26%–62%) in newborns whose mothers had active-chronic or past placental malaria. Thirty-seven mothers (5.3%) and 55 newborns (7.8%) had tetanus antibody levels <0.1 IU/mL (i.e., were seronegative). Mothers' self-reported history of lack of tetanus immunization was the strongest predictor of seronegativity and of tetanus antibody levels in maternal and cord serum.</p>
<p><bold><italic>Conclusion.</italic></bold> Malarial and HIV infections may hinder efforts to eliminate maternal and neonatal tetanus, making implementation of the current policy for mass vaccination of women of childbearing age an urgent priority.</p>
</abstract>
</article-meta>
</front>
<body>
<p>The World Health Organization (WHO) goal for tet-of a lifetime total of 5 doses of TT vaccine to women anus control is to eliminate neonatal tetanus as a public of childbearing age has been recommended [<xref ref-type="bibr" rid="R1">1</xref>]. The health problem by vaccination of women of childbearing effectiveness of maternal TT vaccination in protecting age with tetanus toxoid (TT) vaccine. The schedule orig-newborns against tetanus was shown in vaccine trials inally recommended by the Expanded Programme on in Papua New Guinea [<xref ref-type="bibr" rid="R2">2</xref>] and Colombia [<xref ref-type="bibr" rid="R3">3</xref>]. However, Immunization was 2 doses of TT vaccine during the the field effectiveness of 2 doses of TT vaccine has varied first pregnancy, followed by a booster dose during each widely [<xref ref-type="bibr" rid="R4">4</xref>], and inadequate placental transfer of tetanus subsequent pregnancy. Since 1987, a revised schedule antibodies may contribute to lower-than-expected rates of protection. Factors that potentially affect maternal-fetal transfer of antibodies include preterm birth, placental malaria, and maternal HIV infection [<xref ref-type="bibr" rid="R5">5</xref>–<xref ref-type="bibr" rid="R7">7</xref>].</p>
<p>Although one study has shown no effect of peripheral malarial parasitemia during pregnancy on the response of mothers to TT vaccine in Kenya [<xref ref-type="bibr" rid="R8">8</xref>], results of studies of the effect of placental malaria on maternal-fetal tetanus antibody transfer have been inconsistent. In Papua New Guinea, which has very high malaria transmission, tetanus antibody transfer was substantially lower in women with placental malaria than in women without it, and the authors estimated that ∼10% of babies born to mothers with a heavily infected placenta may not be protected despite adequate maternal antibody concentrations [<xref ref-type="bibr" rid="R9">9</xref>, <xref ref-type="bibr" rid="R10">10</xref>]. In contrast, studies in Malawi [<xref ref-type="bibr" rid="R11">11</xref>] and Gambia [<xref ref-type="bibr" rid="R12">12</xref>] reported no effect of placental malaria on tetanus antibody transfer.</p>
<p>The effect of HIV infection on response to vaccination varies according to age, degree of immunosuppression, and whether primary or recall antibody responses are studied [<xref ref-type="bibr" rid="R13">13</xref>]. Antibody responses to diphtheria toxoid and TT in children with AIDS were absent or lower than those of age-matched control subjects [<xref ref-type="bibr" rid="R14">14</xref>, <xref ref-type="bibr" rid="R15">15</xref>], and from age 2–4 years tetanus and diphtheria antibody levels fell more rapidly in HIV-infected children [<xref ref-type="bibr" rid="R16">16</xref>]. In a small study in Senegal, the response to a booster dose of TT vaccine was significantly lower in HIV-infected than HIVuninfected adults, with little difference between HIV-1 and HIV-2 infection [<xref ref-type="bibr" rid="R17">17</xref>]. In Malawi, in contrast, tetanus antibody levels were similar in HIV-1-infected and HIV-1-uninfected mothers (although TT vaccination status was not reported), and maternofetal tetanus antibody transfer was not significantly reduced in HIV-infected mothers [<xref ref-type="bibr" rid="R11">11</xref>]. Because the prevalence of HIV infection is increasing in large areas of the developing world, it is important to evaluate more fully its potential effect on vaccination programs.</p>
<p>Here, we studied the effect of placental malaria and maternal HIV infection on placental transfer of antibodies to tetanus in Kilifi District, a mainly rural district on the Kenyan coast with perennial transmission of <italic>Plasmodium falciparum</italic> [<xref ref-type="bibr" rid="R18">18</xref>, <xref ref-type="bibr" rid="R19">19</xref>].</p>
<sec sec-type="methods">
<title>Methods</title>
<p>The present study was conducted in the Maternity Department of Kilifi District Hospital and has been described in full elsewhere [<xref ref-type="bibr" rid="R7">7</xref>, <xref ref-type="bibr" rid="R20">20</xref>, <xref ref-type="bibr" rid="R21">21</xref>]. All women delivering between January 1996 and July 1997 were assessed for eligibility to participate. Exclusion criteria were failure to give consent (<2%), twin pregnancy, significant antepartum hemorrhage, and miscarriage. The studies were approved by the Kenya Medical Research Institute/National Ethical Review Committee and the London School of Hygiene and Tropical Medicine.</p>
<p>On admission, a maternal blood sample was obtained. Cord blood was obtained after early clamping and cutting of the cord. The umbilical vein was cleaned and canulated. Plasma was separated and stored at -70°C. Placental smear and biopsy samples were obtained and processed as described elsewhere [<xref ref-type="bibr" rid="R7">7</xref>, <xref ref-type="bibr" rid="R20">20</xref>]. Placental biopsy samples were categorized as one of the following: active-acute malarial infection, for which parasites in maternal erythrocytes in the intervillous space were seen; active-chronic infection, for which malaria pigment, in addition to parasites, was identified in fibrin; past infection, for which malaria pigment alone was seen within fibrin, with no parasites; or negative, for which neither parasites nor pigment were seen [<xref ref-type="bibr" rid="R20">20</xref>]. The HIV status of all women was determined using an IgG antibody-capture particle-adherence test [<xref ref-type="bibr" rid="R22">22</xref>]. After delivery, a standard questionnaire was administered to the women to collect information on pregnancy history, ethnicity, and indicators of socioeconomic status, such as maternal education. Women reported their history of TT vaccination during their current pregnancy; where possible, this was verified from their patient-held antenatal clinic book. Maternal height and weight were measured, and body mass index (BMI) was calculated as the weight in kilograms divided by the square of height in meters. Birth weights were measured on digital scales; babies weighing <2500 g were classified as being of low birth weight. Primigravidae who were recruited into an antimalarial intervention study [<xref ref-type="bibr" rid="R21">21</xref>] underwent an ultrasound scan, which was used to determine gestational age. When a scan was not available, gestational age was estimated postnatally using the assessment of Eregie and Muogbo [<xref ref-type="bibr" rid="R23">23</xref>].</p>
<p>Laboratory assays were performed blinded to maternal HIV status and placental biopsy results. Tetanus antitoxin was measured by an in-house indirect ELISA, which was based on that previously described by Melville-Smith et al. [<xref ref-type="bibr" rid="R24">24</xref>] and Maple et al. [<xref ref-type="bibr" rid="R25">25</xref>]. F96 Nunc-Immuno plates (Maxisorp; Life Technologies) were coated overnight at 4°C with TT (NIBSC) diluted to 0.5 limits of flocculation/mL in carbonate buffer (pH 9.6). At the same time, a set of negative control wells were coated with a solution of 1.0% Marvel (Premier Brands) in carbonate buffer (pH 9.6). The following day, coated plates were washed 3 times with PBS (pH 7.4) containing 0.05% Tween 20 (PBST; Sigma Chemicals), using a Denley microtiter (Wellwash 4) plate washer (Labsystems). All wells were then blocked for 1 h at 37°C with 1% Marvel in PBST and washed 3 times with PBST. Serum samples for testing were diluted in sample buffer (0.1% Marvel in PBST) and tested at dilutions of 1:50, 1:100, 1:200, 1:400, 1:800, and 1:1600. Negative control wells were loaded with serum at 1:50 dilution only. Standard tetanus antitoxin (antitetanus immunoglobulin, human batch 26/488, UK National Institute for Biological Standards and Control) was tested at concentrations of 0.025, 0.012, 0.006, 0.003, 0.0016, and 0.0008 IU/mL in each plate. In addition, one high-and one low-quality control serum sample was run on each plate. After loading, the plates were incubated for 2 h in a humid chamber at 37°C and then washed 3 times with PBST. Conjugate (rabbit anti-human IgG horseradish peroxidase; Sigma A8792) was added and, after incubation for1hat 37°C, plates were washed 3 times with PBST and then 3 times with PBS (pH 7.4). Substrate (ABTS tablets; Sigma A9941 dissolved in citric acid buffer) activated immediately before use with hydrogen peroxide was added, and, after 20–25 min at room temperature, the plates were read at 405 nm using an Anthos 2001 plate reader.</p>
<p>Standard curves were drawn for each plate, and optical densities of test serum dilutions falling within the linear part of the curve were interpolated. The results were expressed as IU per milliliter. The tetanus serology assay is designed to detect levels of antibody in the region of 0.01–0.1 IU/mL. Because antibodies measured by ELISA are not all neutralizing, WHO guidance proposes a cutoff of 0.1–0.2 IU/mL for a protective antibody concentration [<xref ref-type="bibr" rid="R4">4</xref>, <xref ref-type="bibr" rid="R26">26</xref>]. In the present study, an antibody level of 0.1 IU/L was used as the cutoff below which individuals were classified as being seronegative. For antibody levels >10 IU/mL, there is variation, although minor, in the maximum level of detection between assay runs. For samples for which the titer exceeded the maximum level of detection for the assay run, a value twice the maximum titer value for the run was assigned to the sample.</p>
<p>Statistical analyses were performed using Stata (version 8.2; available at: <ext-link ext-link-type="uri" xlink:href="http://www.stata.com">http://www.stata.com</ext-link>. Logarithms of maternal and cord antibody levels were used to calculate geometric mean antibody titers (GMTs) and 95% confidence intervals (CIs). The ratio of the titer in cord serum to that in the respective mother's serum (cord:maternal ratio [CMR]) was used as a measure of placental transfer. Logistic regression was used to estimate the association between placental malaria and tetanus seronegativity and between maternal HIV infection and tetanus seronegativity in the mother and newborn, and linear regression was used to estimate these associations with respect to the log tetanus antibody titers in maternal and cord serum and the log CMRs in seropositive women. The adjusted GMT ratios were calculated using the baseline category as the denominator. Other variables assessed for their relationship with tetanus antibody status were maternal age, parity, postdelivery BMI, gestational age, infant birth weight, ethnic group, and indicators of socioeconomic status (maternal education, literacy, aspects of housing quality, ownership of a working radio, and presence of a latrine). Variables were retained in the model if associations were observed at the <italic>P</italic> < .05 level and/or they altered substantially the associations for other variables in multivariable analysis. Because birth weight and gestational age were highly correlated and, we believe, gestational age is more biologically relevant, only gestational age was retained in the multivariable models. Similarly, parity was retained rather than maternal age, because they were highly correlated and 12% of women had missing data on age. Maternal antibody levels were considered to be on the causal pathway in analyses of cord serum levels and were, thus, excluded from these regression models.</p>
</sec>
<sec sec-type="results">
<title>Results</title>
<p><bold><italic>General characteristics.</italic></bold> Tetanus antibody assays were performed on 725 maternal-cord paired serum samples, of which 21 with missing data on history of TT vaccination were excluded; of the 21 women, 2 (9.5%) were categorized as being seronegative with a GMT of 0.04 (95% CI, 0.002–0.99), whereas the GMT for the seropositive women was 4.23 (95% CI, 2.25–7.97). Of the 704 women in the study, 87 (12%) were HIV positive, 312 (44%) had placental malaria, and 48 (7%) had both. As reported previously [<xref ref-type="bibr" rid="R7">7</xref>, <xref ref-type="bibr" rid="R21">21</xref>], women with active-chronic malarial infection were younger and of lower parity, and their newborns were more likely to be preterm or of low birth weight (data not shown). HIV-positive women were slightly older than HIV-negative women (median age, 23.5 vs. 22.0 years). There were no significant differences in parity, BMI, low birth weight, or preterm delivery between HIV-positive and HIV-negative women.</p>
<p>Forty-four women (6%) reported not having received TT vaccination during the current pregnancy. Of the 660 who reported having received at least 1 dose of TT, 2 gave no information on the number of doses; 332 had received 1 dose, 317 had received 2 doses, and 9 had received 3 doses. Because we lacked information on vaccination history prior to the current pregnancy, we classified women according to receipt or no receipt of any TT doses according to the reported history of vaccination. Reported TT vaccination was not associated with HIV infection or placental malaria (<italic>P</italic> = .83 and <italic>P</italic> = .99, respectively).</p>
<p><bold><italic>Factors associated with tetanus seronegativity and antibody levels in maternal serum.</italic></bold> Overall, only 37 women (5.3%) were negative for tetanus antibodies. These women were younger (median age, 20 years; interquartile range [IQR], 18–22 years) than the tetanus-seropositive women (median age, 22 years; IQR, 19–26 years) (<italic>P</italic> = .001), and 70% were primigravidae. Fourteen tetanus-seronegative women self-reported as having received no vaccine during the current pregnancy, 13 reported receipt of 1 dose, and 10 reported receipt of 2 doses. Data on the timing of vaccination in relation to delivery were not available. TT vaccination status was strongly associated with tetanus seronegativity in mothers, with those who did not receive vaccine during the current pregnancy being 12.5 times more likely than vaccinated women to be seronegative (<xref ref-type="fig" rid="T1">table 1</xref>). Women with 2 or more previous pregnancies were less likely to be seronegative. No other factors had a significant association with maternal tetanus seronegativity.</p>
<p>Overall, the GMT of maternal tetanus antibodies was 2.78 IU/mL (95% CI, 2.5–3.1 IU/mL) (<xref ref-type="fig" rid="T2">table 2</xref>). Tetanus antibody levels were significantly lower in women with active-chronic or past placental malaria, with the adjusted reductions being 36% (95% CI, 12%–53%) and 41% (95% CI, 21%–57%), respectively. Antibody levels were 38% (95% CI, 11%–56%) lower in HIV-infected than HIV-uninfected women (<italic>P</italic> = .009). The GMT of maternal tetanus antibodies in women with both placental malaria and HIV infection was 1.86 IU/mL (95% CI, 1.0–3.2 IU/mL). Antibody levels increased with age and parity, with levels being approximately half as high in primigravidae as multigravidae (<xref ref-type="fig" rid="T2">table 2</xref>). Levels were lower in mothers having preterm deliveries, but the difference was not significant after adjustment for other factors. There were no significant associations between seronegativity or maternal antibody levels and BMI, maternal education, literacy, or other indicators of so-economic status.</p>
<p><bold><italic>Factors associated with placental transfer of tetanus antibodies.</italic></bold> The mean CMR was 0.90 (95% CI, 0.86–0.93) overall (<xref ref-type="fig" rid="T2">table 2</xref>) and was 30% (95% CI, 18%–40%) lower unvaccinated than in vaccinated women. After adjustment for tetanus vaccination and other factors, HIV infection was as sociated with a 22% (95% CI, 13%–31%) reduction in the CMR, and active-chronic and past placental malaria were ascio sociated with 17% (95% CI, 9%–26%) and 11% (95% CI, 1%–19%) reductions, respectively. There was no significant reduction in the CMR with active-acute placental malaria (9% [95% CI, -25% to 11%]). The CMR in women with placental malaria and HIV infection was 0.74 (95% CI, 0.64–0.85). The CMR was 8% (95% CI, -0.1% to 15%) lower in women with low BMI and 15% (95% CI, 4%–24%) lower in women with preterm delivery. CMR was positively associated with maternal antibody concentration, but this association was not significant after adjustment for other factors. There was no strong evidence of association between CMR and maternal age, ethnic group, maternal education, literacy, or other indicators of socioeconomic status.</p>
<p><bold><italic>Factors associated with tetanus seronegativity and antibody levels in cord serum.</italic></bold> Overall, 55 newborns (7.8%) were categorized as being seronegative for tetanus antibody (<xref ref-type="fig" rid="T3">table 3</xref>). Of babies born to tetanus-seronegative mothers, 35 of 37 were seronegative. The 2 babies categorized as being seropositive had tetanus antibody levels of 0.11 and 0.12 IU/mL, and their mothers' tetanus antibody levels were 0.08 and 0.09 IU/mL, respectively. The remaining 20 tetanus-seronegative babies were born to tetanus-seropositive women, who had a median antibody titer of 0.14 (IQR, 0.12–0.18; range, 0.1–0.34), a median age of 19 years (IQR, 18–21.5 years), and 16 (80%) were primigravidae. Four (20%) of the mothers were HIV positive, and 16 (80%) had active-chronic or past placental malaria. Six of the mothers reported not having received TT vaccination during the current pregnancy, 6 reported receiving 1 dose, and 8 reported receiving 2 doses.</p>
<p>Seronegativity in newborns was strongly related to the mother's vaccination status. Of the 44 newborns whose mothers reported not having received TT during the current pregnancy, 19 (43.2%) were seronegative, compared with 5.5% of babies born to vaccinated mothers (<xref ref-type="fig" rid="T3">table 3</xref>). Maternal HIV infection or placental malaria, the mother having <2 previous pregnancies, and not living in a coral house were associated with seronegativity in newborns (<xref ref-type="fig" rid="T3">table 3</xref>).</p>
<p>Tetanus antibody levels in babies born to unvaccinated mothers were less than one-tenth those in babies whose mothers were vaccinated during the current pregnancy (<xref ref-type="fig" rid="T2">table 2</xref>). On multivariable analysis, tetanus antibody levels were 52% (95% CI, 30%–67%) lower in newborns of HIV-infected women, 47% (95% CI, 26%–62%) lower in newborns whose mothers had active-chronic or past placental malaria, 26% (95% CI, 3%–44%) lower in newborns of mothers who were malnourished, and 30% (95% CI, -3% to 52%) lower in preterm babies (<xref ref-type="fig" rid="T2">table 2</xref>). There were no significant interactions between HIV status and placental malaria or vaccination status. Newborns' tetanus antibody levels increased with parity and were 35% (95% CI, 4%–75%) higher among those whose mothers lived in a coral house than among those whose mothers did not. Cord antibody levels were not significantly associated with ethnic group, maternal education, literacy, or other indicators of socioeconomic status.</p>
</sec>
<sec sec-type="discussion">
<title>Discussion</title>
<p>This is the largest study, to our knowledge, of the association between tetanus antibody levels and maternal HIV infection or placental malaria. We found that HIV-infected women had lower tetanus antibody levels, reduced transplacental transfer of tetanus antibody, and ∼50% lower antibody levels in cord serum after adjustment for maternal vaccination and other factors. The decrease in maternal tetanus antibody levels is consistent with data from Senegal [<xref ref-type="bibr" rid="R17">17</xref>] and Brazil [<xref ref-type="bibr" rid="R27">27</xref>] showing reduced responses to TT booster vaccinations in HIV-infected women. A reduction among HIV-infected women in CMR and neonatal tetanus antibody levels has also been reported in Brazil [<xref ref-type="bibr" rid="R28">28</xref>]. A small study in Malawi found no relationship between maternal or cord tetanus antibody levels and HIV; however, no adjustment was made for TT vaccination status [<xref ref-type="bibr" rid="R11">11</xref>].</p>
<p>Maternal and neonatal tetanus antibody levels and transplacental antibody transfer were also reduced when women had active-chronic or past placental malaria. This is similar to findings in Papua New Guinea, where heavy placental infection was associated with a reduction in transfer of tetanus antibodies. Studies in Malawi and The Gambia, however, have reported no effect of placental malaria on tetanus antibodies. These findings may be due to different epidemiological settings and/or different methods used to assess placental malaria. In Malawi, placental smears were used, which are less sensitive than histology when diagnosing chronic or past placental infection because they assess the presence or absence of parasites. In addition, TT vaccination was not controlled for [<xref ref-type="bibr" rid="R11">11</xref>]. In The Gambia [<xref ref-type="bibr" rid="R12">12</xref>], histological examination of the placenta was undertaken, but the sample size was small, and analysis was not done by malarial categories. In The Gambia, there is a single malaria season each year, and the study was undertaken during the malaria season. It may be that pathological changes in the placenta are more likely if the malaria is longer standing and less seasonal. Past or chronic placental malaria is associated with a thickening of basement membrane, inflammatory cell infiltrate, and villitis and so may impair transplacental transfer of antibodies more than acute infection over a longer time.</p>
<p>Similarly, low-density malarial infection may be less likely to affect tetanus antibody transfer than high-level infection [<xref ref-type="bibr" rid="R10">10</xref>, <xref ref-type="bibr" rid="R11">11</xref>]. We found no evidence of modification of the effect of maternal HIV status on tetanus antibody levels by placental malarial status, or vice versa. The pathophysiologic basis for reduced tetanus antibody levels in the 2 conditions is likely to be different (placental pathology in malaria vs. reduced immune responsiveness in HIV infection), and their effects appear not to be multiplicative.</p>
<p>In this hospital-based study in rural Kenya, we found that 5.3% of mothers and 7.8% of newborns were seronegative for tetanus antibody. These results are probably underestimates of the proportion who are seronegative in the general population, because mothers who deliver in the hospital are more likely to have received TT vaccination than are women who deliver at home [<xref ref-type="bibr" rid="R29">29</xref>]. A cutoff of 0.1 IU/mL was used for a protective antibody concentration, which may be considered conservative for an ELISA using titrations of serum that have known neutralizing antibody concentrations, but cases of tetanus have been documented in people with antitoxin concentrations >0.1 IU/mL, and the aim is to sustain immunity well above these thresholds throughout life [<xref ref-type="bibr" rid="R26">26</xref>].</p>
<p>Maternal self-reported history indicating a lack of tetanus immunization was the most important determinant of antibody concentrations in maternal and cord serum. It is difficult to obtain data on a woman's lifetime experience of receipt of TT-containing vaccines, so we could not assess potential variation according to the timing or number of doses received. It is unlikely that many women in our study had received diphtheria-TT-pertussis (DTP) vaccines during infancy or childhood, given that the youngest was born in 1982 and that most were born before 1980, when coverage of DTP in Kenya was <5% and when Kenya did not have a school-based tetanus vaccination program. For most primigravidae in our study, the TT vaccine received in the current pregnancy would therefore have been their primary series of vaccination, whereas for many multigravidae the TT doses would have acted as boosters to doses received in previous pregnancies. It is thus not surprising that 70% of the tetanus-seronegative women were primigravidae and that antibody levels were lower in primigravidae and increased with maternal age. The association between tetanus antibody levels and living in a coral house could also reflect confounding by vaccination, because we could not adjust fully for tetanus vaccination status.</p>
<p>The finding of 13% tetanus seronegativity among babies born to younger women with placental malaria is of concern. This could be an underestimate of the effect of malaria at the population level, given that 57% of primigravidae in our study had been enrolled in a trial of malaria prophylaxis [<xref ref-type="bibr" rid="R21">21</xref>] that reduced the effect of malarial infection among this high-risk group of women.</p>
<p>Malaria and HIV infection may hinder efforts to eliminate maternal and neonatal tetanus, and our findings give further support to the importance of preventing malaria during pregnancy and the current strategy for intermittent preventive treatment for pregnant women living in malaria-endemic areas. Nonetheless, our finding that only 3.6% of women who received TT vaccine during the index pregnancy were seronegative suggests that effective implementation of the current policies for mass vaccination of women of childbearing age should be effective even in areas in which HIV and malaria are prevalent. The WHO has recently expanded the goals of tetanus control to include the prevention of tetanus in all age groups. Booster doses of a TT-containing vaccine are recommended ideally at age 4–7 years and another booster during adolescence (e.g., at age 12–15 years) [<xref ref-type="bibr" rid="R26">26</xref>]. Implementation of this policy, in addition to providing protection to women before their first pregnancy, should assure the long-term maintenance of tetanus immunity.</p>
</sec>
</body>
<back>
<ack>
<title>Acknowledgments</title>
<p>We thank all of the women who participated in this study and all of the people of the Kilifi research unit, particularly Dr. Norbert Peshu, who was head of the Kenya Medical Research Institute in Kilifi; Brett Lowe, who was responsible for managing the laboratory work; Ann Muhoro, Jane Mwendwa, and Judith Peshu, who were midwives; and the study field workers. We also thank Cerys Jones of the Health Protection Agency Centre for Infections (Colindale, London), for performing the indirect ELISA for tetanus antitoxin.</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>Henderson</surname><given-names>RH</given-names></name>
<name><surname>Keja</surname><given-names>J</given-names></name>
<name><surname>Hayden</surname><given-names>G</given-names></name>
<name><surname>Galazka</surname><given-names>A</given-names></name>
<name><surname>Clements</surname><given-names>J</given-names></name>
<name><surname>Chan</surname><given-names>C</given-names></name>
</person-group>
<article-title>Immunizing the children of the world: progress and prospects</article-title>
<source>Bull World Health Organ</source>
<year>1988</year>
<volume>66</volume>
<fpage>535</fpage>
<lpage>43</lpage>
</nlm-citation>
</ref>
<ref id="R2">
<label>2.</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Schofield</surname><given-names>FD</given-names></name>
<name><surname>Tucker</surname><given-names>VM</given-names></name>
<name><surname>Westwook</surname><given-names>GR</given-names></name>
</person-group>
<article-title>Neonatal tetanus in New Guinea</article-title>
<source>BMJ</source>
<year>1961</year>
<volume>2</volume>
<fpage>785</fpage>
<lpage>9</lpage>
</nlm-citation>
</ref>
<ref id="R3">
<label>3.</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Newell</surname><given-names>KW</given-names></name>
<name><surname>Duenas Lehmann</surname><given-names>A</given-names></name>
<name><surname>LeBlanc</surname><given-names>DR</given-names></name>
<name><surname>Garces Osorio</surname><given-names>N</given-names></name>
</person-group>
<article-title>The use of tetanus toxoid for the prevention of neonatal tetanus in developing countries</article-title>
<source>Bull World Health Organ</source>
<year>1966</year>
<volume>35</volume>
<fpage>863</fpage>
<lpage>71</lpage>
</nlm-citation>
</ref>
<ref id="R4">
<label>4.</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Galazka</surname><given-names>A</given-names></name>
</person-group>
<article-title>The immunological basis for immunization series-module</article-title>
<source>Galazka A</source>
</nlm-citation>
</ref>
<ref id="R5">
<label>5.</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Toivanen</surname><given-names>P</given-names></name>
<name><surname>Mantyjarvi</surname><given-names>R</given-names></name>
<name><surname>Hirvoven</surname><given-names>T</given-names></name>
</person-group>
<article-title>Maternal antibodies in human foetal sera at different stages of gestation</article-title>
<source>Immunology</source>
<year>1968</year>
<volume>15</volume>
<fpage>395</fpage>
<lpage>403</lpage>
</nlm-citation>
</ref>
<ref id="R6">
<label>6.</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Gendrel</surname><given-names>D</given-names></name>
<name><surname>Richard-Lenoble</surname><given-names>D</given-names></name>
<name><surname>Massamba</surname><given-names>MB</given-names></name>
<name><surname>Picaud</surname><given-names>A</given-names></name>
<name><surname>Francoual</surname><given-names>C</given-names></name>
<name><surname>Blot</surname><given-names>P</given-names></name>
</person-group>
<article-title>Placental transfer of tetanus antibodies and protection of the newborn</article-title>
<source>J Trop Pediatr</source>
<year>1990</year>
<volume>36</volume>
<fpage>279</fpage>
<lpage>82</lpage>
</nlm-citation>
</ref>
<ref id="R7">
<label>7.</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Scott</surname><given-names>S</given-names></name>
<name><surname>Cumberland</surname><given-names>P</given-names></name>
<name><surname>Shulman</surname><given-names>CE</given-names></name>
<etal></etal>
</person-group>
<article-title>Neonatal measles immunity in rural Kenya: the influence of HIV and placental malaria infections on placental transfer of antibodies and levels of antibody in maternal and cord serum samples</article-title>
<source>J Infect Dis</source>
<year>2005</year>
<volume>191</volume>
<fpage>1854</fpage>
<lpage>60</lpage>
</nlm-citation>
</ref>
<ref id="R8">
<label>8.</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Brabin</surname><given-names>BJ</given-names></name>
</person-group>
<article-title>The influence of malaria and gestation on the immune response to one and two doses of adsorbed tetanus toxoid in pregnancy</article-title>
<source>Bull World Health Organ</source>
<year>1984</year>
<volume>62</volume>
<fpage>919</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>Brabin</surname><given-names>BJ</given-names></name>
<name><surname>Brabin</surname><given-names>L</given-names></name>
<name><surname>Ginny</surname><given-names>M</given-names></name>
<name><surname>Eggelte</surname><given-names>T</given-names></name>
<name><surname>Van der Kaay</surname><given-names>HJ</given-names></name>
<name><surname>Alpers</surname><given-names>MP</given-names></name>
</person-group>
<article-title>Failure of chloroquine prophylaxis in Madang, Papua New Guinea</article-title>
<source>Ann Trop Med Parasitol</source>
<year>1990</year>
<volume>84</volume>
<fpage>1</fpage>
<lpage>9</lpage>
</nlm-citation>
</ref>
<ref id="R10">
<label>10.</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Brair</surname><given-names>M-E</given-names></name>
<name><surname>Brabin</surname><given-names>BJ</given-names></name>
<name><surname>Milligan</surname><given-names>P</given-names></name>
<name><surname>Maxwell</surname><given-names>S</given-names></name>
<name><surname>Hart</surname><given-names>CA</given-names></name>
</person-group>
<article-title>Reduced transfer of tetanus antibodies with placental malaria</article-title>
<source>Lancet</source>
<year>1994</year>
<volume>343</volume>
<fpage>208</fpage>
<lpage>9</lpage>
</nlm-citation>
</ref>
<ref id="R11">
<label>11.</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Moraes-Pinto</surname><given-names>MI</given-names></name>
<name><surname>Verhoeff</surname><given-names>F</given-names></name>
<name><surname>Chimsuku</surname><given-names>L</given-names></name>
<etal></etal>
</person-group>
<article-title>Placental antibody transfer: influence of maternal HIV infection and placental malaria</article-title>
<source>Arch Dis Child Fetal Neonatal Ed</source>
<year>1998</year>
<volume>79</volume>
<fpage>F202</fpage>
<lpage>5</lpage>
</nlm-citation>
</ref>
<ref id="R12">
<label>12.</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Okoko</surname><given-names>BJ</given-names></name>
<name><surname>Lalanga</surname><given-names>H</given-names></name>
<name><surname>Wesumperuma</surname><given-names>L</given-names></name>
<etal></etal>
</person-group>
<article-title>Influence of placental malaria infection and maternal hypergammaglobulinemia on maternofoetal transfer of measles and tetanus antibodies in a rural West African population</article-title>
<source>J Health Popul Nutr</source>
<year>2001</year>
<volume>19</volume>
<fpage>59</fpage>
<lpage>65</lpage>
</nlm-citation>
</ref>
<ref id="R13">
<label>13.</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Moss</surname><given-names>WJ</given-names></name>
<name><surname>Clements</surname><given-names>J</given-names></name>
<name><surname>Halsey</surname><given-names>NA</given-names></name>
</person-group>
<article-title>Immunization of children at risk of infection with human immunodeficiency virus</article-title>
<source>Bull World Health Organ</source>
<year>2003</year>
<volume>81</volume>
<fpage>61</fpage>
<lpage>70</lpage>
</nlm-citation>
</ref>
<ref id="R14">
<label>14.</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Borkowsky</surname><given-names>W</given-names></name>
<name><surname>Steele</surname><given-names>CJ</given-names></name>
<name><surname>Grubman</surname><given-names>S</given-names></name>
<name><surname>Moore</surname><given-names>T</given-names></name>
<name><surname>La Russa</surname><given-names>P</given-names></name>
<name><surname>Kransinski</surname><given-names>K</given-names></name>
</person-group>
<article-title>Antibody responses to bacterial toxoids in children infected with human immunodeficiency virus</article-title>
<source>J Pediatr</source>
<year>1987</year>
<volume>110</volume>
<fpage>563</fpage>
<lpage>6</lpage>
</nlm-citation>
</ref>
<ref id="R15">
<label>15.</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Borkowsky</surname><given-names>W</given-names></name>
<name><surname>Rigaud</surname><given-names>M</given-names></name>
<name><surname>Kransinski</surname><given-names>K</given-names></name>
<name><surname>Moore</surname><given-names>T</given-names></name>
<name><surname>Lawrence</surname><given-names>R</given-names></name>
<name><surname>Pollack</surname><given-names>H</given-names></name>
</person-group>
<article-title>Cell-mediated and humoral immune responses in children infected with human immunodeficiency virus during the first four years of life</article-title>
<source>J Pediatr</source>
<year>1992</year>
<volume>120</volume>
<fpage>371</fpage>
<lpage>5</lpage>
</nlm-citation>
</ref>
<ref id="R16">
<label>16.</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Bernstein</surname><given-names>LJ</given-names></name>
<name><surname>Ochs</surname><given-names>HD</given-names></name>
<name><surname>Wedgewood</surname><given-names>RJ</given-names></name>
<name><surname>Rubinstein</surname><given-names>A</given-names></name>
</person-group>
<article-title>Defective humoral immunity in pediatric acquired immune deficiency syndrome</article-title>
<source>J Pediatr</source>
<year>1985</year>
<volume>107</volume>
<fpage>352</fpage>
<lpage>7</lpage>
</nlm-citation>
</ref>
<ref id="R17">
<label>17.</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Dieye</surname><given-names>TN</given-names></name>
<name><surname>Sow</surname><given-names>PS</given-names></name>
<name><surname>Simonart</surname><given-names>T</given-names></name>
<etal></etal>
</person-group>
<article-title>Immunologic and virologic response after tetanus toxoid booster among HIV-1-and HIV-2-infected Senegalese individuals</article-title>
<source>Vaccine</source>
<year>2001</year>
<volume>20</volume>
<fpage>905</fpage>
<lpage>13</lpage>
</nlm-citation>
</ref>
<ref id="R18">
<label>18.</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Mbogo</surname><given-names>CNM</given-names></name>
<name><surname>Snow</surname><given-names>RW</given-names></name>
<name><surname>Khamala</surname><given-names>CPM</given-names></name>
<etal></etal>
</person-group>
<article-title>Relationship between <italic>Plasmodium falciparum</italic> transmission by vector populations and the incidence of severe disease at nine sites on the Kenyan coast</article-title>
<source>Am J Trop Med Hyg</source>
<year>1995</year>
<volume>52</volume>
<fpage>201</fpage>
<lpage>6</lpage>
</nlm-citation>
</ref>
<ref id="R19">
<label>19.</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Snow</surname><given-names>RW</given-names></name>
<name><surname>Schellenberg</surname><given-names>JR</given-names></name>
<name><surname>Peshu</surname><given-names>N</given-names></name>
<etal></etal>
</person-group>
<article-title>Periodicity and space-time clustering of severe childhood malaria on the coast of Kenya</article-title>
<source>Trans R Soc Trop Med Hyg</source>
<year>1993</year>
<volume>87</volume>
<fpage>386</fpage>
<lpage>90</lpage>
</nlm-citation>
</ref>
<ref id="R20">
<label>20.</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Shulman</surname><given-names>CE</given-names></name>
<name><surname>Marshall</surname><given-names>T</given-names></name>
<name><surname>Dorman</surname><given-names>EK</given-names></name>
<etal></etal>
</person-group>
<article-title>Malaria in pregnancy: adverse effects on haemoglobin levels and birthweight in primigravidae and multigravidae</article-title>
<source>Trop Med Int Health</source>
<year>2001</year>
<volume>6</volume>
<fpage>770</fpage>
<lpage>8</lpage>
</nlm-citation>
</ref>
<ref id="R21">
<label>21.</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Shulman</surname><given-names>CE</given-names></name>
<name><surname>Dorman</surname><given-names>EK</given-names></name>
<name><surname>Cutts</surname><given-names>F</given-names></name>
<etal></etal>
</person-group>
<article-title>Intermittent sulphadoxinepyrimethamine to prevent severe anaemia secondary to malaria in pregnancy: a randomised placebo-controlled trial</article-title>
<source>Lancet</source>
<year>1999</year>
<volume>353</volume>
<fpage>632</fpage>
<lpage>6</lpage>
</nlm-citation>
</ref>
<ref id="R22">
<label>22.</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Parry</surname><given-names>JV</given-names></name>
<name><surname>Mortimer</surname><given-names>PP</given-names></name>
</person-group>
<article-title>An immunoglobulin G antibody capture particle-adherence test (GACPAT) for antibody to HIV-1 and HTLV-1 that allows economical large-scale screening</article-title>
<source>AIDS</source>
<year>1989</year>
<volume>3</volume>
<fpage>173</fpage>
<lpage>6</lpage>
</nlm-citation>
</ref>
<ref id="R23">
<label>23.</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Eregie</surname><given-names>CO</given-names></name>
<name><surname>Muogbo</surname><given-names>DC</given-names></name>
</person-group>
<article-title>A simplified method of estimating gestational age in an African population</article-title>
<source>Dev Med Child Neurol</source>
<year>1991</year>
<volume>33</volume>
<fpage>146</fpage>
<lpage>52</lpage>
</nlm-citation>
</ref>
<ref id="R24">
<label>24.</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Melville-Smith</surname><given-names>ME</given-names></name>
<name><surname>Seagrott</surname><given-names>VA</given-names></name>
<name><surname>Watkins</surname><given-names>JT</given-names></name>
</person-group>
<article-title>A comparison of enzyme-linked immunosorbent assay (ELISA) with the toxin neutralization test in mice as a method for the estimation of tetanus antitoxin in human sera</article-title>
<source>J Biol Stand</source>
<year>1983</year>
<volume>11</volume>
<fpage>137</fpage>
<lpage>44</lpage>
</nlm-citation>
</ref>
<ref id="R25">
<label>25.</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Maple</surname><given-names>PA</given-names></name>
<name><surname>Jones</surname><given-names>CS</given-names></name>
<name><surname>Wall</surname><given-names>EC</given-names></name>
<etal></etal>
</person-group>
<article-title>Immunity to diphtheria and tetanus in England and Wales</article-title>
<source>Vaccine</source>
<year>2000</year>
<volume>19</volume>
<fpage>167</fpage>
<lpage>73</lpage>
</nlm-citation>
</ref>
<ref id="R26">
<label>26.</label>
<nlm-citation citation-type="journal">
<collab>World Health Organization</collab>
<article-title>Tetanus vaccine</article-title>
<source>Wkly Epidemiol Rec</source>
<year>2006</year>
<volume>81</volume>
<fpage>198</fpage>
<lpage>208</lpage>
</nlm-citation>
</ref>
<ref id="R27">
<label>27.</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Bonetti</surname><given-names>TCS</given-names></name>
<name><surname>Succi</surname><given-names>RCM</given-names></name>
<name><surname>Weckx</surname><given-names>LY</given-names></name>
<name><surname>Tavares-opes</surname><given-names>L</given-names></name>
<name><surname>Moraes-Pinto</surname><given-names>MI</given-names></name>
</person-group>
<article-title>Tetanus and diphtheria antibodies and response to a booster dose in Brazilian HIV-1-infected women</article-title>
<source>Vaccine</source>
<year>2004</year>
<volume>22</volume>
<fpage>3707</fpage>
<lpage>12</lpage>
</nlm-citation>
</ref>
<ref id="R28">
<label>28.</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>de Moraes-Pinto</surname><given-names>MI</given-names></name>
<name><surname>Almeida</surname><given-names>AC</given-names></name>
<name><surname>Kenj</surname><given-names>G</given-names></name>
<etal></etal>
</person-group>
<article-title>Placental transfer and maternally acquired neonatal IgG immunity in human immunodeficiency virus infection</article-title>
<source>J Infect Dis</source>
<year>1996</year>
<volume>173</volume>
<fpage>1077</fpage>
<lpage>84</lpage>
</nlm-citation>
</ref>
<ref id="R29">
<label>29.</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Cutts</surname><given-names>FT</given-names></name>
<name><surname>Rodrigues</surname><given-names>LC</given-names></name>
<name><surname>Colombo</surname><given-names>S</given-names></name>
<name><surname>Bennett</surname><given-names>S</given-names></name>
</person-group>
<article-title>Evaluation of factors influencing vaccine uptake in Mozambique</article-title>
<source>Int J Epidemiol</source>
<year>1989</year>
<volume>18</volume>
<fpage>427</fpage>
<lpage>33</lpage>
</nlm-citation>
</ref>
</ref-list>
<sec sec-type="display-objects">
<title>Figures and Tables</title>
<fig id="T1" position="float">
<label>Table 1.</label>
<caption><p>Factors associated with maternal serum tetanus antibody levels <0.1 IU/mL (seronegative).</p></caption>
<graphic mimetype="image" xlink:href="196-4-550-tbl001.tif"></graphic>
</fig>
<fig id="T2" position="float">
<label>Table 2.</label>
<caption><p>Tetanus antibody titers in maternal and cord serum and cord:maternal ratio (CMR), by maternal HIV status, placental malaria, and other factors.</p></caption>
<graphic mimetype="image" xlink:href="196-4-550-tbl002.tif"></graphic>
</fig>
<fig id="T3" position="float">
<label>Table 3.</label>
<caption><p>Factors associated with cord serum tetanus antibody levels <0.1 IU/mL (seronegative).</p></caption>
<graphic mimetype="image" xlink:href="196-4-550-tbl003.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: UK Department of International Development; Kenya Medical Research Institute; Wellcome Trust (support to the study and grant 63342 to K.M.).</p>
</fn>
<fn fn-type="other">
<p>This study is published with the permission of the director of the Kenya Medical Research Institute.</p>
</fn>
</fn-group>
</back>
</article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo><title>Maternal HIV Infection and Placental Malaria Reduce Transplacental Antibody Transfer and Tetanus Antibody Levels in Newborns in Kenya</title></titleInfo><titleInfo type="alternative" contentType="CDATA"><title>Maternal HIV Infection and Placental Malaria Reduce Transplacental Antibody Transfer and Tetanus Antibody Levels in Newborns in Kenya</title></titleInfo><name type="personal"><namePart type="given">Phillippa</namePart><namePart type="family">Cumberland</namePart><affiliation>Centre for Paediatric Epidemiology and Biostatistics, Institute of Child Health, London</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Caroline E.</namePart><namePart type="family">Shulman</namePart><affiliation>Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London</affiliation><affiliation>Kenya Medical Research Institute, Centre for Geographical Medicine Research-Coast, Kilifi, Kenya</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">P. A.</namePart><namePart type="family">Chris Maple</namePart><affiliation>Virus Reference Department, Health Protection Agency Centre for Infections, London</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Judith N.</namePart><namePart type="family">Bulmer</namePart><affiliation>School of Clinical and Laboratory Sciences (Pathology), Newcastle University, Newcastle upon Tyne, United Kingdom</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Edgar K.</namePart><namePart type="family">Dorman</namePart><affiliation>Homerton University Hospital NHS Foundation Trust, London</affiliation><affiliation>Kenya Medical Research Institute, Centre for Geographical Medicine Research-Coast, Kilifi, Kenya</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Ken</namePart><namePart type="family">Kawuondo</namePart><affiliation>Kenya Medical Research Institute, Centre for Geographical Medicine Research-Coast, Kilifi, Kenya</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Kevin</namePart><namePart type="family">Marsh</namePart><affiliation>Kenya Medical Research Institute, Centre for Geographical Medicine Research-Coast, Kilifi, Kenya</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal" displayLabel="corresp"><namePart type="given">Felicity T.</namePart><namePart type="family">Cutts</namePart><affiliation>Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London</affiliation><affiliation>E-mail: felicity.cutts@lshtm.ac.uk</affiliation><affiliation>Reprints or correspondence: Felicity Cutts London School of Hygiene and Tropical Medicine Keppel St. London WC1 7HT UK</affiliation><affiliation>E-mail: felicity.cutts@lshtm.ac.uk</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">2007-08-15</dateIssued><copyrightDate encoding="w3cdtf">2007</copyrightDate></originInfo><abstract>Background. In clinical trials, maternal tetanus toxoid (TT) vaccination is effective in protecting newborns against tetanus infection, but inadequate placental transfer of tetanus antibodies may contribute to lower-thanexpected rates of protection in routine practice. We studied the effect of placental malaria and maternal human immunodeficiency virus (HIV) infection on placental transfer of antibodies to tetanus. Methods. A total of 704 maternal-cord paired serum samples were tested by ELISA for antibodies to tetanus. The HIV status of all women was determined by an immunoglobulin G antibody-capture particle-adherence test, and placental malaria was determined by placental biopsy. Maternal history of TT vaccination was recorded. Results. Tetanus antibody levels were reduced by 52% (95% confidence interval [CI], 30%–67%) in newborns of HIV-infected women and by 48% (95% CI, 26%–62%) in newborns whose mothers had active-chronic or past placental malaria. Thirty-seven mothers (5.3%) and 55 newborns (7.8%) had tetanus antibody levels <0.1 IU/mL (i.e., were seronegative). Mothers' self-reported history of lack of tetanus immunization was the strongest predictor of seronegativity and of tetanus antibody levels in maternal and cord serum. Conclusion. Malarial and HIV infections may hinder efforts to eliminate maternal and neonatal tetanus, making implementation of the current policy for mass vaccination of women of childbearing age an urgent priority.</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>HIV/AIDS</topic></subject><subject><topic>Major Article</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>4</number></detail><extent unit="pages"><start>550</start><end>557</end></extent></part></relatedItem><identifier type="istex">88C118EFCA60DB4F8740D8E73E965AF1B408762C</identifier><identifier type="DOI">10.1086/519845</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/88C118EFCA60DB4F8740D8E73E965AF1B408762C/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/88C118EFCA60DB4F8740D8E73E965AF1B408762C/covers/tiff</uri></json:item><json:item><extension>html</extension><original>true</original><mimetype>text/html</mimetype><uri>https://api.istex.fr/document/88C118EFCA60DB4F8740D8E73E965AF1B408762C/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/88C118EFCA60DB4F8740D8E73E965AF1B408762C/annexes/jpeg</uri></json:item><json:item><extension>gif</extension><original>true</original><mimetype>image/gif</mimetype><uri>https://api.istex.fr/document/88C118EFCA60DB4F8740D8E73E965AF1B408762C/annexes/gif</uri></json:item></annexes><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/SidaSubSaharaV1/Data/Istex/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 002C68 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Istex/Corpus/biblio.hfd -nk 002C68 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Sante
|area= SidaSubSaharaV1
|flux= Istex
|étape= Corpus
|type= RBID
|clé= ISTEX:88C118EFCA60DB4F8740D8E73E965AF1B408762C
|texte= Maternal HIV Infection and Placental Malaria Reduce Transplacental Antibody Transfer and Tetanus Antibody Levels in Newborns in Kenya
}}
| This area was generated with Dilib version V0.6.32. |  |