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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Associations Between Maternal Helminth and Malaria Infections in Pregnancy and Clinical Malaria in the Offspring: A Birth Cohort in Entebbe, Uganda</title><author><name sortKey="Ndibazza, Juliet" sort="Ndibazza, Juliet" uniqKey="Ndibazza J" first="Juliet" last="Ndibazza">Juliet Ndibazza</name><affiliation><nlm:aff id="af1"><institution>MRC/UVRI Uganda Research Unit on AIDS</institution></nlm:aff></affiliation></author><author><name sortKey="Webb, Emily L" sort="Webb, Emily L" uniqKey="Webb E" first="Emily L." last="Webb">Emily L. Webb</name><affiliation><nlm:aff id="af3"><institution>London School of Hygiene and Tropical Medicine</institution>,<country>United Kingdom</country></nlm:aff></affiliation></author><author><name sortKey="Lule, Swaib" sort="Lule, Swaib" uniqKey="Lule S" first="Swaib" last="Lule">Swaib Lule</name><affiliation><nlm:aff id="af1"><institution>MRC/UVRI Uganda Research Unit on AIDS</institution></nlm:aff></affiliation></author><author><name sortKey="Mpairwe, Harriet" sort="Mpairwe, Harriet" uniqKey="Mpairwe H" first="Harriet" last="Mpairwe">Harriet Mpairwe</name><affiliation><nlm:aff id="af1"><institution>MRC/UVRI Uganda Research Unit on AIDS</institution></nlm:aff></affiliation></author><author><name sortKey="Akello, Miriam" sort="Akello, Miriam" uniqKey="Akello M" first="Miriam" last="Akello">Miriam Akello</name><affiliation><nlm:aff id="af2"><institution>Entebbe Hospital</institution>,<addr-line>Entebbe</addr-line>,<country>Uganda</country></nlm:aff></affiliation></author><author><name sortKey="Oduru, Gloria" sort="Oduru, Gloria" uniqKey="Oduru G" first="Gloria" last="Oduru">Gloria Oduru</name><affiliation><nlm:aff id="af2"><institution>Entebbe Hospital</institution>,<addr-line>Entebbe</addr-line>,<country>Uganda</country></nlm:aff></affiliation></author><author><name sortKey="Kizza, Moses" sort="Kizza, Moses" uniqKey="Kizza M" first="Moses" last="Kizza">Moses Kizza</name><affiliation><nlm:aff id="af1"><institution>MRC/UVRI Uganda Research Unit on AIDS</institution></nlm:aff></affiliation></author><author><name sortKey="Akurut, Helen" sort="Akurut, Helen" uniqKey="Akurut H" first="Helen" last="Akurut">Helen Akurut</name><affiliation><nlm:aff id="af1"><institution>MRC/UVRI Uganda Research Unit on AIDS</institution></nlm:aff></affiliation></author><author><name sortKey="Muhangi, Lawrence" sort="Muhangi, Lawrence" uniqKey="Muhangi L" first="Lawrence" last="Muhangi">Lawrence Muhangi</name><affiliation><nlm:aff id="af1"><institution>MRC/UVRI Uganda Research Unit on AIDS</institution></nlm:aff></affiliation></author><author><name sortKey="Magnussen, Pascal" sort="Magnussen, Pascal" uniqKey="Magnussen P" first="Pascal" last="Magnussen">Pascal Magnussen</name><affiliation><nlm:aff id="af4"><addr-line>Institute for International Health, Immunology and Microbiology, Faculty of Health and Medical Sciences</addr-line></nlm:aff></affiliation></author><author><name sortKey="Vennervald, Birgitte" sort="Vennervald, Birgitte" uniqKey="Vennervald B" first="Birgitte" last="Vennervald">Birgitte Vennervald</name><affiliation><nlm:aff id="af5"><addr-line>Section for Parasitology and Aquatic Diseases, Faculty of Health and Medical Sciences</addr-line>,<institution>Copenhagen University</institution>,<country>Denmark</country></nlm:aff></affiliation></author><author><name sortKey="Elliott, Alison" sort="Elliott, Alison" uniqKey="Elliott A" first="Alison" last="Elliott">Alison Elliott</name><affiliation><nlm:aff id="af1"><institution>MRC/UVRI Uganda Research Unit on AIDS</institution></nlm:aff></affiliation><affiliation><nlm:aff id="af3"><institution>London School of Hygiene and Tropical Medicine</institution>,<country>United Kingdom</country></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">23904293</idno><idno type="pmc">3836463</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836463</idno><idno type="RBID">PMC:3836463</idno><idno type="doi">10.1093/infdis/jit397</idno><date when="2013">2013</date><idno type="wicri:Area/Pmc/Corpus">002679</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002679</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Associations Between Maternal Helminth and Malaria Infections in Pregnancy and Clinical Malaria in the Offspring: A Birth Cohort in Entebbe, Uganda</title><author><name sortKey="Ndibazza, Juliet" sort="Ndibazza, Juliet" uniqKey="Ndibazza J" first="Juliet" last="Ndibazza">Juliet Ndibazza</name><affiliation><nlm:aff id="af1"><institution>MRC/UVRI Uganda Research Unit on AIDS</institution></nlm:aff></affiliation></author><author><name sortKey="Webb, Emily L" sort="Webb, Emily L" uniqKey="Webb E" first="Emily L." last="Webb">Emily L. Webb</name><affiliation><nlm:aff id="af3"><institution>London School of Hygiene and Tropical Medicine</institution>,<country>United Kingdom</country></nlm:aff></affiliation></author><author><name sortKey="Lule, Swaib" sort="Lule, Swaib" uniqKey="Lule S" first="Swaib" last="Lule">Swaib Lule</name><affiliation><nlm:aff id="af1"><institution>MRC/UVRI Uganda Research Unit on AIDS</institution></nlm:aff></affiliation></author><author><name sortKey="Mpairwe, Harriet" sort="Mpairwe, Harriet" uniqKey="Mpairwe H" first="Harriet" last="Mpairwe">Harriet Mpairwe</name><affiliation><nlm:aff id="af1"><institution>MRC/UVRI Uganda Research Unit on AIDS</institution></nlm:aff></affiliation></author><author><name sortKey="Akello, Miriam" sort="Akello, Miriam" uniqKey="Akello M" first="Miriam" last="Akello">Miriam Akello</name><affiliation><nlm:aff id="af2"><institution>Entebbe Hospital</institution>,<addr-line>Entebbe</addr-line>,<country>Uganda</country></nlm:aff></affiliation></author><author><name sortKey="Oduru, Gloria" sort="Oduru, Gloria" uniqKey="Oduru G" first="Gloria" last="Oduru">Gloria Oduru</name><affiliation><nlm:aff id="af2"><institution>Entebbe Hospital</institution>,<addr-line>Entebbe</addr-line>,<country>Uganda</country></nlm:aff></affiliation></author><author><name sortKey="Kizza, Moses" sort="Kizza, Moses" uniqKey="Kizza M" first="Moses" last="Kizza">Moses Kizza</name><affiliation><nlm:aff id="af1"><institution>MRC/UVRI Uganda Research Unit on AIDS</institution></nlm:aff></affiliation></author><author><name sortKey="Akurut, Helen" sort="Akurut, Helen" uniqKey="Akurut H" first="Helen" last="Akurut">Helen Akurut</name><affiliation><nlm:aff id="af1"><institution>MRC/UVRI Uganda Research Unit on AIDS</institution></nlm:aff></affiliation></author><author><name sortKey="Muhangi, Lawrence" sort="Muhangi, Lawrence" uniqKey="Muhangi L" first="Lawrence" last="Muhangi">Lawrence Muhangi</name><affiliation><nlm:aff id="af1"><institution>MRC/UVRI Uganda Research Unit on AIDS</institution></nlm:aff></affiliation></author><author><name sortKey="Magnussen, Pascal" sort="Magnussen, Pascal" uniqKey="Magnussen P" first="Pascal" last="Magnussen">Pascal Magnussen</name><affiliation><nlm:aff id="af4"><addr-line>Institute for International Health, Immunology and Microbiology, Faculty of Health and Medical Sciences</addr-line></nlm:aff></affiliation></author><author><name sortKey="Vennervald, Birgitte" sort="Vennervald, Birgitte" uniqKey="Vennervald B" first="Birgitte" last="Vennervald">Birgitte Vennervald</name><affiliation><nlm:aff id="af5"><addr-line>Section for Parasitology and Aquatic Diseases, Faculty of Health and Medical Sciences</addr-line>,<institution>Copenhagen University</institution>,<country>Denmark</country></nlm:aff></affiliation></author><author><name sortKey="Elliott, Alison" sort="Elliott, Alison" uniqKey="Elliott A" first="Alison" last="Elliott">Alison Elliott</name><affiliation><nlm:aff id="af1"><institution>MRC/UVRI Uganda Research Unit on AIDS</institution></nlm:aff></affiliation><affiliation><nlm:aff id="af3"><institution>London School of Hygiene and Tropical Medicine</institution>,<country>United Kingdom</country></nlm:aff></affiliation></author></analytic><series><title level="j">The Journal of Infectious Diseases</title><idno type="ISSN">0022-1899</idno><idno type="eISSN">1537-6613</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><bold><italic>Background.</italic></bold> Helminth and malaria coinfections are common in the tropics. We investigated the hypothesis that prenatal exposure to these parasites might influence susceptibility to malaria in childhood.</p><p><bold><italic>Methods.</italic></bold> In a birth cohort of 2345 mother–child pairs in Uganda, maternal helminth and malaria infection status was determined during pregnancy, and childhood malaria episodes were recorded from birth to age 5 years. We examined associations between maternal infections and malaria in the offspring.</p><p><bold><italic>Results.</italic></bold> Common maternal infections were hookworm (45%), <italic>Mansonella perstans</italic> (21%), <italic>Schistosoma mansoni</italic> (18%), and <italic>Plasmodium falciparum</italic> (11%). At age 5 years, 69% of the children were still under follow-up. The incidence of malaria was 34 episodes per 100 child-years, and the mean prevalence of asymptomatic malaria at annual visits was 5.4%. Maternal hookworm and <italic>M. perstans</italic> infections were associated with an increased rate of childhood clinical malaria (adjusted hazard ratio [aHR], 1.24, 95% confidence interval [CI], 1.10–1.41; aHR, 1.20, 95% CI, 1.05–1.38, respectively). <italic>S. mansoni</italic> infection had no consistent association with childhood malaria.</p><p><bold><italic>Conclusions.</italic></bold> This is the first report of an association between helminth infections in pregnancy and malaria in the offspring and indicates that helminth infections in pregnancy may increase the burden of childhood malaria morbidity.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Brooker, S" uniqKey="Brooker S">S Brooker</name></author><author><name sortKey="Akhwale, W" uniqKey="Akhwale W">W Akhwale</name></author><author><name sortKey="Pullan, R" uniqKey="Pullan R">R Pullan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mazigo, Hd" uniqKey="Mazigo H">HD Mazigo</name></author><author><name sortKey="Waihenya, R" uniqKey="Waihenya R">R Waihenya</name></author><author><name sortKey="Lwambo, Nj" uniqKey="Lwambo N">NJ Lwambo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mwangi, Tw" uniqKey="Mwangi T">TW Mwangi</name></author><author><name sortKey="Bethony, Jm" uniqKey="Bethony J">JM Bethony</name></author><author><name sortKey="Brooker, S" uniqKey="Brooker S">S Brooker</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Silva, Nr" uniqKey="De Silva N">NR de Silva</name></author><author><name sortKey="Brooker, S" uniqKey="Brooker S">S Brooker</name></author><author><name sortKey="Hotez, Pj" uniqKey="Hotez P">PJ Hotez</name></author><author><name sortKey="Montresor, A" uniqKey="Montresor A">A Montresor</name></author><author><name sortKey="Engels, D" uniqKey="Engels D">D Engels</name></author><author><name sortKey="Savioli, L" uniqKey="Savioli L">L Savioli</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Snow, Rw" uniqKey="Snow R">RW Snow</name></author><author><name sortKey="Guerra, Ca" uniqKey="Guerra C">CA Guerra</name></author><author><name sortKey="Noor, Am" uniqKey="Noor A">AM Noor</name></author><author><name sortKey="Myint, Hy" uniqKey="Myint H">HY Myint</name></author><author><name sortKey="Hay, Si" uniqKey="Hay S">SI Hay</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Desai, M" uniqKey="Desai M">M Desai</name></author><author><name sortKey="Ter Kuile, Fo" uniqKey="Ter Kuile F">FO ter Kuile</name></author><author><name sortKey="Nosten, F" uniqKey="Nosten F">F Nosten</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Steketee, Rw" uniqKey="Steketee R">RW Steketee</name></author><author><name sortKey="Nahlen, Bl" uniqKey="Nahlen B">BL Nahlen</name></author><author><name sortKey="Parise, Me" uniqKey="Parise M">ME Parise</name></author><author><name sortKey="Menendez, C" uniqKey="Menendez C">C Menendez</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Le Hesran, Jy" uniqKey="Le Hesran J">JY Le Hesran</name></author><author><name sortKey="Cot, M" uniqKey="Cot M">M Cot</name></author><author><name sortKey="Personne, P" uniqKey="Personne P">P Personne</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Malhotra, I" uniqKey="Malhotra I">I Malhotra</name></author><author><name sortKey="Dent, A" uniqKey="Dent A">A Dent</name></author><author><name sortKey="Mungai, P" uniqKey="Mungai P">P Mungai</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bundy, Da" uniqKey="Bundy D">DA Bundy</name></author><author><name sortKey="Chan, Ms" uniqKey="Chan M">MS Chan</name></author><author><name sortKey="Savioli, L" uniqKey="Savioli L">L Savioli</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Christian, P" uniqKey="Christian P">P Christian</name></author><author><name sortKey="Khatry, Sk" uniqKey="Khatry S">SK Khatry</name></author><author><name sortKey="West, Kp" uniqKey="West K">KP West</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Friedman, Jf" uniqKey="Friedman J">JF Friedman</name></author><author><name sortKey="Mital, P" uniqKey="Mital P">P Mital</name></author><author><name sortKey="Kanzaria, Hk" uniqKey="Kanzaria H">HK Kanzaria</name></author><author><name sortKey="Olds, Gr" uniqKey="Olds G">GR Olds</name></author><author><name sortKey="Kurtis, Jd" uniqKey="Kurtis J">JD Kurtis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Muhangi, L" uniqKey="Muhangi L">L Muhangi</name></author><author><name sortKey="Woodburn, P" uniqKey="Woodburn P">P Woodburn</name></author><author><name sortKey="Omara, M" uniqKey="Omara M">M Omara</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ndibazza, J" uniqKey="Ndibazza J">J Ndibazza</name></author><author><name sortKey="Muhangi, L" uniqKey="Muhangi L">L Muhangi</name></author><author><name sortKey="Akishule, D" uniqKey="Akishule D">D Akishule</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Adegnika, Aa" uniqKey="Adegnika A">AA Adegnika</name></author><author><name sortKey="Ramharter, M" uniqKey="Ramharter M">M Ramharter</name></author><author><name sortKey="Agnandji, St" uniqKey="Agnandji S">ST Agnandji</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hillier, Sd" uniqKey="Hillier S">SD Hillier</name></author><author><name sortKey="Booth, M" uniqKey="Booth M">M Booth</name></author><author><name sortKey="Muhangi, L" uniqKey="Muhangi L">L Muhangi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Briand, V" uniqKey="Briand V">V Briand</name></author><author><name sortKey="Watier, L" uniqKey="Watier L">L Watier</name></author><author><name sortKey="Jy, Leh" uniqKey="Jy L">LEH JY</name></author><author><name sortKey="Garcia, A" uniqKey="Garcia A">A Garcia</name></author><author><name sortKey="Cot, M" uniqKey="Cot M">M Cot</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Spiegel, A" uniqKey="Spiegel A">A Spiegel</name></author><author><name sortKey="Tall, A" uniqKey="Tall A">A Tall</name></author><author><name sortKey="Raphenon, G" uniqKey="Raphenon G">G Raphenon</name></author><author><name sortKey="Trape, Jf" uniqKey="Trape J">JF Trape</name></author><author><name sortKey="Druilhe, P" uniqKey="Druilhe P">P Druilhe</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Boel, M" uniqKey="Boel M">M Boel</name></author><author><name sortKey="Carrara, Vi" uniqKey="Carrara V">VI Carrara</name></author><author><name sortKey="Rijken, M" uniqKey="Rijken M">M Rijken</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Midzi, N" uniqKey="Midzi N">N Midzi</name></author><author><name sortKey="Sangweme, D" uniqKey="Sangweme D">D Sangweme</name></author><author><name sortKey="Zinyowera, S" uniqKey="Zinyowera S">S Zinyowera</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hartgers, Fc" uniqKey="Hartgers F">FC Hartgers</name></author><author><name sortKey="Yazdanbakhsh, M" uniqKey="Yazdanbakhsh M">M Yazdanbakhsh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Maizels, Rm" uniqKey="Maizels R">RM Maizels</name></author><author><name sortKey="Balic, A" uniqKey="Balic A">A Balic</name></author><author><name sortKey="Gomez Escobar, N" uniqKey="Gomez Escobar N">N Gomez-Escobar</name></author><author><name sortKey="Nair, M" uniqKey="Nair M">M Nair</name></author><author><name sortKey="Taylor, Md" uniqKey="Taylor M">MD Taylor</name></author><author><name sortKey="Allen, Je" uniqKey="Allen J">JE Allen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Su, Z" uniqKey="Su Z">Z Su</name></author><author><name sortKey="Segura, M" uniqKey="Segura M">M Segura</name></author><author><name sortKey="Morgan, K" uniqKey="Morgan K">K Morgan</name></author><author><name sortKey="Loredo Osti, Jc" uniqKey="Loredo Osti J">JC Loredo-Osti</name></author><author><name sortKey="Stevenson, Mm" uniqKey="Stevenson M">MM Stevenson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Riet, E" uniqKey="Van Riet E">E van Riet</name></author><author><name sortKey="Hartgers, Fc" uniqKey="Hartgers F">FC Hartgers</name></author><author><name sortKey="Yazdanbakhsh, M" uniqKey="Yazdanbakhsh M">M Yazdanbakhsh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hewitson, Jp" uniqKey="Hewitson J">JP Hewitson</name></author><author><name sortKey="Grainger, Jr" uniqKey="Grainger J">JR Grainger</name></author><author><name sortKey="Maizels, Rm" uniqKey="Maizels R">RM Maizels</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Helmby, H" uniqKey="Helmby H">H Helmby</name></author><author><name sortKey="Kullberg, M" uniqKey="Kullberg M">M Kullberg</name></author><author><name sortKey="Troye Blomberg, M" uniqKey="Troye Blomberg M">M Troye-Blomberg</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Novato Silva, E" uniqKey="Novato Silva E">E Novato-Silva</name></author><author><name sortKey="Gazzinelli, G" uniqKey="Gazzinelli G">G Gazzinelli</name></author><author><name sortKey="Colley, Dg" uniqKey="Colley D">DG Colley</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Druilhe, P" uniqKey="Druilhe P">P Druilhe</name></author><author><name sortKey="Tall, A" uniqKey="Tall A">A Tall</name></author><author><name sortKey="Sokhna, C" uniqKey="Sokhna C">C Sokhna</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nacher, M" uniqKey="Nacher M">M Nacher</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Elliott, Am" uniqKey="Elliott A">AM Elliott</name></author><author><name sortKey="Kizza, M" uniqKey="Kizza M">M Kizza</name></author><author><name sortKey="Quigley, Ma" uniqKey="Quigley M">MA Quigley</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Okello, Pe" uniqKey="Okello P">PE Okello</name></author><author><name sortKey="Van Bortel, W" uniqKey="Van Bortel W">W Van Bortel</name></author><author><name sortKey="Byaruhanga, Am" uniqKey="Byaruhanga A">AM Byaruhanga</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Melrose, W" uniqKey="Melrose W">W Melrose</name></author><author><name sortKey="Pisters, P" uniqKey="Pisters P">P Pisters</name></author><author><name sortKey="Turner, P" uniqKey="Turner P">P Turner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Katz, N" uniqKey="Katz N">N Katz</name></author><author><name sortKey="Chaves, A" uniqKey="Chaves A">A Chaves</name></author><author><name sortKey="Pellegrino, J" uniqKey="Pellegrino J">J Pellegrino</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bukusuba, Jw" uniqKey="Bukusuba J">JW Bukusuba</name></author><author><name sortKey="Hughes, P" uniqKey="Hughes P">P Hughes</name></author><author><name sortKey="Kizza, M" uniqKey="Kizza M">M Kizza</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ndibazza, J" uniqKey="Ndibazza J">J Ndibazza</name></author><author><name sortKey="Mpairwe, H" uniqKey="Mpairwe H">H Mpairwe</name></author><author><name sortKey="Webb, El" uniqKey="Webb E">EL Webb</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Adegnika, Aa" uniqKey="Adegnika A">AA Adegnika</name></author><author><name sortKey="Kremsner, Pg" uniqKey="Kremsner P">PG Kremsner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Woodburn, Pw" uniqKey="Woodburn P">PW Woodburn</name></author><author><name sortKey="Muhangi, L" uniqKey="Muhangi L">L Muhangi</name></author><author><name sortKey="Hillier, S" uniqKey="Hillier S">S Hillier</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Brutus, L" uniqKey="Brutus L">L Brutus</name></author><author><name sortKey="Watier, L" uniqKey="Watier L">L Watier</name></author><author><name sortKey="Hanitrasoamampionona, V" uniqKey="Hanitrasoamampionona V">V Hanitrasoamampionona</name></author><author><name sortKey="Razanatsoarilala, H" uniqKey="Razanatsoarilala H">H Razanatsoarilala</name></author><author><name sortKey="Cot, M" uniqKey="Cot M">M Cot</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sokhna, C" uniqKey="Sokhna C">C Sokhna</name></author><author><name sortKey="Le Hesran, Jy" uniqKey="Le Hesran J">JY Le Hesran</name></author><author><name sortKey="Mbaye, Pa" uniqKey="Mbaye P">PA Mbaye</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wilson, S" uniqKey="Wilson S">S Wilson</name></author><author><name sortKey="Vennervald, Bj" uniqKey="Vennervald B">BJ Vennervald</name></author><author><name sortKey="Kadzo, H" uniqKey="Kadzo H">H Kadzo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Diallo, To" uniqKey="Diallo T">TO Diallo</name></author><author><name sortKey="Remoue, F" uniqKey="Remoue F">F Remoue</name></author><author><name sortKey="Schacht, Am" uniqKey="Schacht A">AM Schacht</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mutabingwa, Tk" uniqKey="Mutabingwa T">TK Mutabingwa</name></author><author><name sortKey="Bolla, Mc" uniqKey="Bolla M">MC Bolla</name></author><author><name sortKey="Li, Jl" uniqKey="Li J">JL Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Schwarz, Ng" uniqKey="Schwarz N">NG Schwarz</name></author><author><name sortKey="Adegnika, Aa" uniqKey="Adegnika A">AA Adegnika</name></author><author><name sortKey="Breitling, Lp" uniqKey="Breitling L">LP Breitling</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sangweme, Dt" uniqKey="Sangweme D">DT Sangweme</name></author><author><name sortKey="Midzi, N" uniqKey="Midzi N">N Midzi</name></author><author><name sortKey="Zinyowera Mutapuri, S" uniqKey="Zinyowera Mutapuri S">S Zinyowera-Mutapuri</name></author><author><name sortKey="Mduluza, T" uniqKey="Mduluza T">T Mduluza</name></author><author><name sortKey="Diener West, M" uniqKey="Diener West M">M Diener-West</name></author><author><name sortKey="Kumar, N" uniqKey="Kumar N">N Kumar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bonner, Pc" uniqKey="Bonner P">PC Bonner</name></author><author><name sortKey="Zhou, Z" uniqKey="Zhou Z">Z Zhou</name></author><author><name sortKey="Mirel, Lb" uniqKey="Mirel L">LB Mirel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nossal, Gj" uniqKey="Nossal G">GJ Nossal</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bradley, Dj" uniqKey="Bradley D">DJ Bradley</name></author><author><name sortKey="May, Rm" uniqKey="May R">RM May</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Breitling, Lp" uniqKey="Breitling L">LP Breitling</name></author><author><name sortKey="Wilson, Aj" uniqKey="Wilson A">AJ Wilson</name></author><author><name sortKey="Raiko, A" uniqKey="Raiko A">A Raiko</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ellis, Mk" uniqKey="Ellis M">MK Ellis</name></author><author><name sortKey="Mcmanus, Dp" uniqKey="Mcmanus D">DP McManus</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chico, Rm" uniqKey="Chico R">RM Chico</name></author><author><name sortKey="Mayaud, P" uniqKey="Mayaud P">P Mayaud</name></author><author><name sortKey="Ariti, C" uniqKey="Ariti C">C Ariti</name></author><author><name sortKey="Mabey, D" uniqKey="Mabey D">D Mabey</name></author><author><name sortKey="Ronsmans, C" uniqKey="Ronsmans C">C Ronsmans</name></author><author><name sortKey="Chandramohan, D" uniqKey="Chandramohan D">D Chandramohan</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">J Infect Dis</journal-id><journal-id journal-id-type="iso-abbrev">J. Infect. Dis</journal-id><journal-id journal-id-type="publisher-id">jid</journal-id><journal-id journal-id-type="hwp">jinfdis</journal-id><journal-title-group><journal-title>The Journal of Infectious Diseases</journal-title></journal-title-group><issn pub-type="ppub">0022-1899</issn><issn pub-type="epub">1537-6613</issn><publisher><publisher-name>Oxford University Press</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">23904293</article-id><article-id pub-id-type="pmc">3836463</article-id><article-id pub-id-type="doi">10.1093/infdis/jit397</article-id><article-id pub-id-type="publisher-id">jit397</article-id><article-categories><subj-group subj-group-type="heading"><subject>Major Articles and Brief Reports</subject><subj-group subj-group-type="heading"><subject>Parasites</subject></subj-group></subj-group></article-categories><title-group><article-title>Associations Between Maternal Helminth and Malaria Infections in Pregnancy and Clinical Malaria in the Offspring: A Birth Cohort in Entebbe, Uganda</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Ndibazza</surname><given-names>Juliet</given-names></name><xref ref-type="aff" rid="af1">1</xref></contrib><contrib contrib-type="author"><name><surname>Webb</surname><given-names>Emily L.</given-names></name><xref ref-type="aff" rid="af3">3</xref></contrib><contrib contrib-type="author"><name><surname>Lule</surname><given-names>Swaib</given-names></name><xref ref-type="aff" rid="af1">1</xref></contrib><contrib contrib-type="author"><name><surname>Mpairwe</surname><given-names>Harriet</given-names></name><xref ref-type="aff" rid="af1">1</xref></contrib><contrib contrib-type="author"><name><surname>Akello</surname><given-names>Miriam</given-names></name><xref ref-type="aff" rid="af2">2</xref></contrib><contrib contrib-type="author"><name><surname>Oduru</surname><given-names>Gloria</given-names></name><xref ref-type="aff" rid="af2">2</xref></contrib><contrib contrib-type="author"><name><surname>Kizza</surname><given-names>Moses</given-names></name><xref ref-type="aff" rid="af1">1</xref></contrib><contrib contrib-type="author"><name><surname>Akurut</surname><given-names>Helen</given-names></name><xref ref-type="aff" rid="af1">1</xref></contrib><contrib contrib-type="author"><name><surname>Muhangi</surname><given-names>Lawrence</given-names></name><xref ref-type="aff" rid="af1">1</xref></contrib><contrib contrib-type="author"><name><surname>Magnussen</surname><given-names>Pascal</given-names></name><xref ref-type="aff" rid="af4">4</xref></contrib><contrib contrib-type="author"><name><surname>Vennervald</surname><given-names>Birgitte</given-names></name><xref ref-type="aff" rid="af5">5</xref></contrib><contrib contrib-type="author"><name><surname>Elliott</surname><given-names>Alison</given-names></name><xref ref-type="aff" rid="af1">1</xref><xref ref-type="aff" rid="af3">3</xref></contrib></contrib-group><aff id="af1"><label>1</label><institution>MRC/UVRI Uganda Research Unit on AIDS</institution></aff><aff id="af2"><label>2</label><institution>Entebbe Hospital</institution>,<addr-line>Entebbe</addr-line>,<country>Uganda</country></aff><aff id="af3"><label>3</label><institution>London School of Hygiene and Tropical Medicine</institution>,<country>United Kingdom</country></aff><aff id="af4"><label>4</label><addr-line>Institute for International Health, Immunology and Microbiology, Faculty of Health and Medical Sciences</addr-line></aff><aff id="af5"><label>5</label><addr-line>Section for Parasitology and Aquatic Diseases, Faculty of Health and Medical Sciences</addr-line>,<institution>Copenhagen University</institution>,<country>Denmark</country></aff><author-notes><fn><p>Presented in part: 61st Annual meeting of the American Society of Tropical Medicine and Hygiene, Atlanta, Georgia, 13 November 2012. Poster 875.</p></fn><corresp id="cor1">Correspondence: Juliet Ndibazza, MBChB, MSc, MRC/UVRI Uganda Research Unit on AIDS, PO Box 49, Entebbe, Uganda (<email>jnbazza@yahoo.com</email>).</corresp></author-notes><pub-date pub-type="ppub"><day>15</day><month>12</month><year>2013</year></pub-date><pub-date pub-type="epub"><day>31</day><month>7</month><year>2013</year></pub-date><pub-date pub-type="pmc-release"><day>31</day><month>7</month><year>2013</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on the
<volume>208</volume><issue>12</issue><fpage>2007</fpage><lpage>2016</lpage><history><date date-type="received"><day>18</day><month>3</month><year>2013</year></date><date date-type="accepted"><day>11</day><month>6</month><year>2013</year></date></history><permissions><copyright-statement>© The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.</copyright-statement><copyright-year>2013</copyright-year><license license-type="creative-commons" xlink:href="http://creativecommons.org/licenses/by/3.0/"><license-p><pmc-comment>CREATIVE COMMONS</pmc-comment>This is an Open Access article distributed under the terms of the Creative Commons Attribution License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/3.0/">http://creativecommons.org/licenses/by/3.0/</ext-link>), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p></license></permissions><self-uri content-type="pdf" xlink:type="simple" xlink:href="jit397.pdf"></self-uri><abstract><p><bold><italic>Background.</italic></bold> Helminth and malaria coinfections are common in the tropics. We investigated the hypothesis that prenatal exposure to these parasites might influence susceptibility to malaria in childhood.</p><p><bold><italic>Methods.</italic></bold> In a birth cohort of 2345 mother–child pairs in Uganda, maternal helminth and malaria infection status was determined during pregnancy, and childhood malaria episodes were recorded from birth to age 5 years. We examined associations between maternal infections and malaria in the offspring.</p><p><bold><italic>Results.</italic></bold> Common maternal infections were hookworm (45%), <italic>Mansonella perstans</italic> (21%), <italic>Schistosoma mansoni</italic> (18%), and <italic>Plasmodium falciparum</italic> (11%). At age 5 years, 69% of the children were still under follow-up. The incidence of malaria was 34 episodes per 100 child-years, and the mean prevalence of asymptomatic malaria at annual visits was 5.4%. Maternal hookworm and <italic>M. perstans</italic> infections were associated with an increased rate of childhood clinical malaria (adjusted hazard ratio [aHR], 1.24, 95% confidence interval [CI], 1.10–1.41; aHR, 1.20, 95% CI, 1.05–1.38, respectively). <italic>S. mansoni</italic> infection had no consistent association with childhood malaria.</p><p><bold><italic>Conclusions.</italic></bold> This is the first report of an association between helminth infections in pregnancy and malaria in the offspring and indicates that helminth infections in pregnancy may increase the burden of childhood malaria morbidity.</p></abstract><kwd-group><kwd>malaria</kwd><kwd>helminths</kwd><kwd>coinfections</kwd><kwd>pregnancy</kwd><kwd>childhood</kwd></kwd-group></article-meta></front><body><p>Chronic infection with <italic>Plasmodium</italic> and helminths causes an enormous public health burden in the tropics [<xref ref-type="bibr" rid="JIT397C1">1</xref>–<xref ref-type="bibr" rid="JIT397C5">5</xref>]. Malaria in pregnancy has been associated with increased risk of maternal anemia, low birth weight, stillbirth, and maternal death [<xref ref-type="bibr" rid="JIT397C6">6</xref>, <xref ref-type="bibr" rid="JIT397C7">7</xref>]. Recent evidence suggests that prenatal exposure to <italic>Plasmodium falciparum</italic> may increase malaria risk in early childhood [<xref ref-type="bibr" rid="JIT397C8">8</xref>, <xref ref-type="bibr" rid="JIT397C9">9</xref>]; however, little is known about the long-term consequences for young children.</p><p>In the 1990s, estimates suggested that 44 million of the world's pregnant women harbored hookworm [<xref ref-type="bibr" rid="JIT397C10">10</xref>], and it was suggested that helminth infections might be particularly detrimental to the mother during pregnancy [<xref ref-type="bibr" rid="JIT397C11">11</xref>, <xref ref-type="bibr" rid="JIT397C12">12</xref>]. However, in the Entebbe Mother and Baby Study (EMaBS) we found unexpectedly little association between maternal helminths and maternal anemia and none of the expected benefits of anthelminthic treatment in pregnancy for birth outcomes [<xref ref-type="bibr" rid="JIT397C13">13</xref>, <xref ref-type="bibr" rid="JIT397C14">14</xref>]. Still, there is a dearth of literature on the consequences of helminth infections in pregnancy for the child, and effects of prenatal exposure to malaria<italic>–</italic>helminth coinfections on childhood malaria have not been addressed.</p><p>Studies including the EMaBS have reported associations between malaria and helminth infections in pregnant women [<xref ref-type="bibr" rid="JIT397C15">15</xref>, <xref ref-type="bibr" rid="JIT397C16">16</xref>], and others have reported associations in children [<xref ref-type="bibr" rid="JIT397C17">17</xref>, <xref ref-type="bibr" rid="JIT397C18">18</xref>]. Hookworm infection has been related to increased susceptibility to malaria infection in pregnancy [<xref ref-type="bibr" rid="JIT397C2">2</xref>, <xref ref-type="bibr" rid="JIT397C16">16</xref>, <xref ref-type="bibr" rid="JIT397C19">19</xref>] and in children [<xref ref-type="bibr" rid="JIT397C2">2</xref>, <xref ref-type="bibr" rid="JIT397C20">20</xref>]. However, results have been inconsistent [<xref ref-type="bibr" rid="JIT397C15">15</xref>, <xref ref-type="bibr" rid="JIT397C21">21</xref>]. Immunoregulatory mechanisms have been proposed. Helminth infections induce T-cell hyporesponsiveness, downmodulating immunity to their own as well as other antigens [<xref ref-type="bibr" rid="JIT397C22">22</xref>–<xref ref-type="bibr" rid="JIT397C25">25</xref>], and <italic>Plasmodia</italic> may possibly modulate responses to helminth coinfections [<xref ref-type="bibr" rid="JIT397C26">26</xref>]. Prenatal exposure to pathogen antigens might enhance fetal tolerance or sensitization to the antigens, leading to a failure to mount a response to the infection [<xref ref-type="bibr" rid="JIT397C9">9</xref>] or the development of infection resistance [<xref ref-type="bibr" rid="JIT397C27">27</xref>], respectively. Whether such immunological effects have a measurable impact on the incidence of malaria is uncertain [<xref ref-type="bibr" rid="JIT397C28">28</xref>, <xref ref-type="bibr" rid="JIT397C29">29</xref>].</p><p>In the EMaBS, treatment with anthelminthics in pregnancy had no effect on childhood malaria incidence. However, we speculated that the single-dose treatment might be insufficient to change an effect of helminths established earlier during pregnancy. This study used EMaBS data (ISRCTN32849447) [<xref ref-type="bibr" rid="JIT397C30">30</xref>] to examine associations between helminth and malaria infections in pregnancy and malaria in the offspring.</p><sec sec-type="methods" id="s2"><title>METHODS</title><p>The study was approved by the Science and Ethics Committee of the Uganda Virus Research Institute, the Uganda National Council for Science and Technology and the ethics committee of the London School of Hygiene and Tropical Medicine. Project staff explained the study to the participants in the local language and provided participants with a study information letter to take home. Written informed consent was obtained from the mother during pregnancy and from the mother or caregiver when the child was aged 1 year.</p><sec id="s2a"><title>Study Population</title><p>The study area is on the northern shores of Lake Victoria in Uganda, a high malaria transmission area. <italic>P. falciparum</italic> is the dominant <italic>Plasmodium</italic> species; <italic>Anopheles gambiae</italic> and <italic>Anopheles fenestus</italic> are the dominant vectors [<xref ref-type="bibr" rid="JIT397C31">31</xref>]. The area consists of urban, rural, and fishing communities.</p></sec><sec id="s2b"><title>Study Design</title><p>The EMaBS enrolled 2507 pregnant women in their second or third trimester between April 2003 and November 2005; 2345 live births were recorded. Inclusion and exclusion criteria are described elsewhere [<xref ref-type="bibr" rid="JIT397C30">30</xref>]. We present an observational analysis of the trial cohort.</p><p>At enrolment, the median gestational age was 27 weeks (interquartile range, 22–31). Before receiving the trial intervention, women gave a blood and stool sample for assessment of parasite infections. Women were then randomized to single-dose albendazole (400 mg) or placebo, and praziquantel (40 mg/kg) or placebo; their offspring were randomized to receive quarterly single-dose albendazole (200 mg from age 15 to 21 months and 400 mg from age 24 to 60 months) or placebo. Ferrous sulphate was provided monthly, and intermittent presumptive treatment for malaria (sulphadoxine-pyrimethamine) twice during the pregnancy. All women received anthelminthic treatment 6 weeks after delivery. After delivery, mothers were invited to bring the children to the research clinic for routine immunizations and any illness and for quarterly study visits to age 5 years. Community workers visited the children fortnightly and referred sick children to the clinic. Clinical malaria episodes were recorded prospectively. At annual scheduled visits, the children were examined for <italic>P. falciparum</italic> and helminth infections and were treated according to clinical guidelines if infections were found.</p><p>Participants' addresses at enrollment were geo-referenced using handheld GPS receivers, and geographical zones were established based on features such as coastline, forest, location of settlements, and altitude [<xref ref-type="bibr" rid="JIT397C16">16</xref>].</p></sec><sec id="s2c"><title>Diagnosis of Infections</title><p>Women provided blood and stool samples at enrollment and after delivery; children provided samples at illness and routine annual visits. Blood samples were examined for <italic>Mansonella perstans</italic> using the modified Knott's method [<xref ref-type="bibr" rid="JIT397C32">32</xref>]. Thick blood films were stained with Leishman's stain, malaria parasites were counted against 200 leucocytes, and at least 100 high-power fields were examined before a film was declared negative. Duplicate Kato–Katz slides were prepared and examined within 30 minutes for hookworm and the following day for other helminth eggs [<xref ref-type="bibr" rid="JIT397C33">33</xref>, <xref ref-type="bibr" rid="JIT397C34">34</xref>]. Human immunodeficiency virus (HIV) serology was performed for mothers and children aged ≥18 months using a rapid test algorithm [<xref ref-type="bibr" rid="JIT397C13">13</xref>]; for infants, RNA and DNA polymerase chain reaction methods were used. Vector Control Division, Ministry of Health, Uganda, provided quality control for Kato–Katz slides, and the Medical Research Council Laboratories at Uganda Virus Research Institute provide quality control for malaria films.</p></sec><sec id="s2d"><title>Statistical Methods</title><p>The aim was to examine the association between maternal helminth and malaria infections in pregnancy and malaria in the offspring. The sample size for the study was determined for the original trial objectives. To test the hypothesis that maternal albendazole or praziquantel in pregnancy would influence the incidence of malaria in infancy (assumed to be 0.5 per person-year in the maternal placebo group), a study with 2500 participants would have 80% power to show an 18% reduction or a 19% increase in the incidence of malaria in infancy, with <italic>P</italic> < .05, assuming that each intervention had an independent effect. Either direction of effect could happen, depending on whether helminth coinfection increases susceptibility to malaria infection and disease or decreases inflammation and hence reduces malaria-induced morbidity.</p><p>Of 2345 live births, 53 twins and 3 triplets were excluded, leaving 2289 children for inclusion in the analysis. Primary outcome was incidence of childhood clinical malaria from birth to age 5 years, and secondary outcome was prevalence of asymptomatic <italic>P. falciparum</italic> parasitemia as determined at annual visits to age 5 years. Childhood clinical malaria was defined as a history of recent fever or axillary temperature of ≥37.5°C and any parasitemia. Asymptomatic <italic>P. falciparum</italic> parasitemia was defined as a positive malaria slide in the absence of fever on the sampling day. Key predictor variables were maternal <italic>P. falciparum</italic>, hookworm, <italic>M. perstans,</italic> and <italic>S. mansoni</italic> infections at enrollment<italic>.</italic> Malaria was defined as peripheral parasitemia.</p><p>For the primary outcome, time at risk began at birth and was censored at loss to follow-up, death, or age 5 years. Clinical malaria episodes within 14 days of an initial presentation were regarded as a recrudescence and excluded from the analysis; time at risk was adjusted accordingly, excluding these 14-day periods from the total person-time denominator. Crude hazard ratios (HRs) for the effect of malaria and helminth infections in pregnancy on the incidence of childhood malaria were calculated using Cox regression with robust standard errors to allow for within-child clustering of malaria episodes. Independent risk factors for maternal infections and childhood malaria that were significant (<italic>P</italic> ≤ .10) at the univariable analyses were entered into multivariable models. Variables included in the models were maternal age, education, parity, HIV status, mosquito net ownership, socioeconomic status, and geographical residential zone. Maternal <italic>P. falciparum</italic> and HIV infections and child albendazole were assessed as potential effect modifiers of the association between each maternal infection and childhood malaria. The secondary outcome was analyzed by combining data from all annual visits and comparing repeated prevalence of parasitemia between maternal malaria and helminth infection groups using random effects logistic regression, adjusting for the same confounders. Adjusted <italic>P</italic> values were calculated using likelihood ratio tests. Albendazole and praziquantel treatment in pregnancy had no effect on the incidence of clinical malaria [<xref ref-type="bibr" rid="JIT397C35">35</xref>]; hence there was no need to allow for them in the analysis. Statistical analysis was performed using Stata version 11. Rather than formally adjusting for multiple testing, we interpreted consistent results for related outcomes as providing evidence of a true association. Significance was defined as <italic>P</italic> values ≤ .05.</p></sec></sec><sec sec-type="results" id="s3"><title>RESULTS</title><p>Of 2345 live births, 1622 children (69%) were still under follow-up at 5 years, and a total of 33 178 clinic visits for illnesses were recorded [<xref ref-type="bibr" rid="JIT397C35">35</xref>]. A trial flow chart has been reported previously [<xref ref-type="bibr" rid="JIT397C35">35</xref>] and is available as <ext-link ext-link-type="uri" xlink:href="http://jid.oxfordjournals.org/lookup/suppl/doi:10.1093/infdis/jit397/-/DC1">Supplementary Figure 1</ext-link>. The total number of clinic visits was similar across maternal helminth groups (data not shown). Table <xref ref-type="table" rid="JIT397TB1">1</xref> shows characteristics of the participating women and children. A complete description of maternal infections in pregnancy, previously reported [<xref ref-type="bibr" rid="JIT397C36">36</xref>], is provided in <ext-link ext-link-type="uri" xlink:href="http://jid.oxfordjournals.org/lookup/suppl/doi:10.1093/infdis/jit397/-/DC1">Supplementary Appendix 1</ext-link>. The overall mean <italic>P. falciparum</italic> parasite count in pregnancy was 163 (standard deviation [SD], 357), and only 51 (22%) of 236 mothers with parasitemia had >1000 parasite/µL blood. Two hundred two (8%) women were infected with <italic>P. falciparum</italic> and at least one of hookworm or <italic>S. mansoni</italic> or <italic>M. perstans</italic>. At delivery, only 69 of 2133 (3%) of the women tested had malaria parasitemia. Maternal HIV prevalence was 11%.
<table-wrap id="JIT397TB1" position="float"><label>Table 1.</label><caption><p>Characteristics of Mothers and Children Who Participated in the Study</p></caption><table frame="hsides" rules="groups"><colgroup span="1"><col align="left" span="1"></col><col align="left" span="1"></col><col align="char" char="(" span="1"></col></colgroup><thead><tr><th align="left" rowspan="1" colspan="1">Group</th><th align="left" rowspan="1" colspan="1">Characteristic</th><th align="left" rowspan="1" colspan="1">Summary</th></tr></thead><tbody><tr><td rowspan="1" colspan="1">Mothers (n = 2289)</td><td rowspan="1" colspan="1">Mean age (±SD) at enrollment Gravidity</td><td rowspan="1" colspan="1">24 (5.4)</td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"> 1</td><td rowspan="1" colspan="1">611 (27%)</td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"> 2–4</td><td rowspan="1" colspan="1">1307 (57%)</td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"> ≥5</td><td rowspan="1" colspan="1">371 (16%)</td></tr><tr><td rowspan="1" colspan="1"></td><td colspan="2" rowspan="1">Trimester (4 mv)</td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"> 2</td><td rowspan="1" colspan="1">1051 (46%)</td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"> 3</td><td rowspan="1" colspan="1">1234 (54%)</td></tr><tr><td rowspan="1" colspan="1"></td><td colspan="2" rowspan="1">Highest educational level attained (4mv)</td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"> None</td><td rowspan="1" colspan="1">81 (4%)</td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"> Primary</td><td rowspan="1" colspan="1">1152 (50%)</td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"> Secondary</td><td rowspan="1" colspan="1">860 (38%)</td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"> Tertiary</td><td rowspan="1" colspan="1">192 (8%)</td></tr><tr><td rowspan="1" colspan="1"></td><td colspan="2" rowspan="1">Socioeconomic status (44 mv)</td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"> Lower</td><td rowspan="1" colspan="1">1028 (45%)</td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"> Higher</td><td rowspan="1" colspan="1">1217 (53%)</td></tr><tr><td rowspan="1" colspan="1"></td><td colspan="2" rowspan="1">Infections</td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"> Any helminth (29 mv)</td><td rowspan="1" colspan="1">1545 (68%)</td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"> Hookworm (9 mv)</td><td rowspan="1" colspan="1">1004 (45%)</td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"> <italic>Schistosoma mansoni</italic> (9 mv)</td><td rowspan="1" colspan="1">415 (18%)</td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"> <italic>Mansonella perstans</italic> (8 mv)</td><td rowspan="1" colspan="1">492 (21%)</td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"> <italic>Plasmodium falciparum</italic> (43 mv)</td><td rowspan="1" colspan="1">236 (10%)</td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"> HIV</td><td rowspan="1" colspan="1">261 (11%)</td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">Received IPTp</td><td rowspan="1" colspan="1">2211 (97%)</td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">Owns mosquito net</td><td rowspan="1" colspan="1">1131 (49%)</td></tr><tr><td rowspan="1" colspan="1"></td><td colspan="2" rowspan="1">Primary source of water (5 mv)</td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"> Open source</td><td rowspan="1" colspan="1">1910 (83%)</td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"> Piped source</td><td rowspan="1" colspan="1">374 (16%)</td></tr><tr><td rowspan="1" colspan="1"></td><td colspan="2" rowspan="1">Primary source of fuel (6 mv)</td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"> Firewood</td><td rowspan="1" colspan="1">408 (18%)</td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"> Charcoal</td><td rowspan="1" colspan="1">1626 (71%)</td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"> Paraffin</td><td rowspan="1" colspan="1">49 (2%)</td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"> Gas/electricity</td><td rowspan="1" colspan="1">200 (9%)</td></tr><tr><td rowspan="1" colspan="1">Children (n = 2289)</td><td rowspan="1" colspan="1">Male</td><td rowspan="1" colspan="1">1167 (51%)</td></tr><tr><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">Mean birthweight (±SD)</td><td rowspan="1" colspan="1">3.19 (±0.49)</td></tr></tbody></table><table-wrap-foot><fn><p>Abbreviations: HIV, human immunodeficiency virus; IPTp, intermittent presumptive treatment for malaria; mv, missing values; SD, standard deviation.</p></fn></table-wrap-foot></table-wrap></p><p>The prevalence of helminth infections was low among the children: 2.9% (95% confidence interval [CI], 2.0–3.8), 5.2% (95% CI, 4.0–6.3), 7.7% (95% CI, 6.3–9.1), 9.0% (95% CI, 7.4–10.5), and 9.5% (95% CI, 7.9–11.1) at annual visits 1, 2, 3, 4, and 5 years, respectively. Of 2289 children, 1161 (51%) had at least 1 malaria episode; 459 (20%) had 1 episode, and 702 (31%) had ≥2 episodes (18 children had >10 episodes). The overall malaria incidence rate was 34 per 100 child-years, higher in the first 2 years (41 and 53 per 100 child-years, respectively), than in years 3, 4, and 5 (31, 20, and 20 per 100 child-years, respectively). The annual prevalence of asymptomatic parasitemia among the children was 5.9% (95% CI, 4.8–7.2), 7.1% (95% CI, 5.9–8.5), 4.7% 95% CI, (3.7–6.0), 4.3% (95% CI, 3.3–5.6) and 4.8% (95% CI, 3.8–6.1) at 1, 2, 3, 4, and 5 years, respectively. The overall mean parasite density was 8292 parasites/µL (SD, 18 576).</p><sec id="s3a"><title>Variables Associated With Helminth and Malaria Infections in Pregnancy</title><p>Older age, higher education, higher socioeconomic status, and mosquito net ownership were associated with a lower prevalence of maternal helminth and malaria infections [<xref ref-type="bibr" rid="JIT397C37">37</xref>]. HIV infection was negatively associated with hookworm, whereas HIV, hookworm, and <italic>M. perstans</italic> infections were associated with increased odds of maternal malaria. The risk of maternal helminth and malaria infection in pregnancy varied significantly by geographical zone [<xref ref-type="bibr" rid="JIT397C16">16</xref>].</p></sec><sec id="s3b"><title>Variables Associated With Childhood Malaria</title><p>Table <xref ref-type="table" rid="JIT397TB2">2</xref> shows that children of younger, poorer mothers, who had a low education level and did not own a mosquito net had a higher risk of childhood clinical malaria. The risk also varied significantly by both parity and geographical location of residence.
<table-wrap id="JIT397TB2" position="float"><label>Table 2.</label><caption><p>Variables Associated With Clinical Malaria Episodes in Childhood (aged 0–5 years)</p></caption><table frame="hsides" rules="groups"><colgroup span="1"><col align="left" span="1"></col><col align="char" char="(" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col></colgroup><thead><tr><th align="left" rowspan="1" colspan="1">Maternal Risk Factor</th><th align="left" rowspan="1" colspan="1">Incidence Rate per 100 Child-Years (95% CI)</th><th align="left" rowspan="1" colspan="1">Crude HR (95% CI)</th><th align="left" rowspan="1" colspan="1">Adjusted HR<sup>a</sup> (95% CI)</th><th align="left" rowspan="1" colspan="1"><italic>P</italic> Value</th></tr></thead><tbody><tr><td colspan="5" rowspan="1">Age (years)</td></tr><tr><td rowspan="1" colspan="1"> <25</td><td rowspan="1" colspan="1">34.70 (33.21–36.26)</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"> ≥25</td><td rowspan="1" colspan="1">32.57 (30.79–34.45)</td><td rowspan="1" colspan="1">0.94 (.83–1.08)</td><td rowspan="1" colspan="1">0.84 (.71–.99)</td><td rowspan="1" colspan="1">.04</td></tr><tr><td colspan="5" rowspan="1">Parity</td></tr><tr><td rowspan="1" colspan="1"> Primipara</td><td rowspan="1" colspan="1">31.78 (29.60–34.11)</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"> Multipara (2–4)</td><td rowspan="1" colspan="1">32.83 (31.35–34.39)</td><td rowspan="1" colspan="1">1.04 (.90–1.20)</td><td rowspan="1" colspan="1">1.13 (.97–1.30)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"> Grand multipara ( ≥5)</td><td rowspan="1" colspan="1">40.55 (37.53–43.80)</td><td rowspan="1" colspan="1">1.29 (1.06–1.57)</td><td rowspan="1" colspan="1">1.40 (1.10–1.78)</td><td rowspan="1" colspan="1">.03</td></tr><tr><td colspan="5" rowspan="1">HIV</td></tr><tr><td rowspan="1" colspan="1"> Negative</td><td rowspan="1" colspan="1">34.38 (33.15–35.64)</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"> Positive</td><td rowspan="1" colspan="1">29.21 (25.96–32.86)</td><td rowspan="1" colspan="1">0.85 (.68–1.06)</td><td rowspan="1" colspan="1">0.82 (.67–1.01)</td><td rowspan="1" colspan="1">.14</td></tr><tr><td colspan="5" rowspan="1">Socioeconomic</td></tr><tr><td rowspan="1" colspan="1"> Lower status</td><td rowspan="1" colspan="1">37.57 (35.76–39.48)</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"> Higher status</td><td rowspan="1" colspan="1">30.30 (28.82–31.85)</td><td rowspan="1" colspan="1">0.81 (.71–.92)</td><td rowspan="1" colspan="1">0.85 (.75–.96)</td><td rowspan="1" colspan="1">.01</td></tr><tr><td colspan="5" rowspan="1">Education</td></tr><tr><td rowspan="1" colspan="1"> None/Primary</td><td rowspan="1" colspan="1">39.01 (37.32–40.78)</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"> Postprimary</td><td rowspan="1" colspan="1">28.12 (26.60–29.73)</td><td rowspan="1" colspan="1">0.73 (.64–.82)</td><td rowspan="1" colspan="1">0.83 (.73–.94)</td><td rowspan="1" colspan="1">.003</td></tr><tr><td colspan="5" rowspan="1">Owns bed net</td></tr><tr><td rowspan="1" colspan="1">Yes</td><td rowspan="1" colspan="1">27.00 (25.55–28.53)</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1">.01</td></tr><tr><td rowspan="1" colspan="1">No</td><td rowspan="1" colspan="1">40.67 (38.90–42.52)</td><td rowspan="1" colspan="1">1.50 (1.32–1.71)</td><td rowspan="1" colspan="1">1.17 (1.04–1.33)</td><td rowspan="1" colspan="1"></td></tr><tr><td colspan="5" rowspan="1">Water source</td></tr><tr><td rowspan="1" colspan="1">Piped</td><td rowspan="1" colspan="1">29.93 (28.75–31.17)</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">Open</td><td rowspan="1" colspan="1">53.10 (49.63–56.82)</td><td rowspan="1" colspan="1">1.78 (1.54–2.06)</td><td rowspan="1" colspan="1">1.39 (1.19–1.61)</td><td rowspan="1" colspan="1"><.001</td></tr><tr><td colspan="5" rowspan="1">Fuel source</td></tr><tr><td rowspan="1" colspan="1">Indoor (electricity/gas)</td><td rowspan="1" colspan="1">14.30 (11.92–17.16)</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">Outdoor (paraffin/charcoal/wood)</td><td rowspan="1" colspan="1">35.79 (34.55–37.08)</td><td rowspan="1" colspan="1">2.53 (2.01–3.18)</td><td rowspan="1" colspan="1">1.83 (1.44–2.32)</td><td rowspan="1" colspan="1"><.001</td></tr><tr><td rowspan="1" colspan="1">Geographical zone</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1">15.19 (13.04–17.69)</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">2</td><td rowspan="1" colspan="1">19.32 (16.87–22.13)</td><td rowspan="1" colspan="1">1.26 (.93–1.71)</td><td rowspan="1" colspan="1">1.57 (1.15–2.13)</td><td rowspan="1" colspan="1"><.001</td></tr><tr><td rowspan="1" colspan="1">3</td><td rowspan="1" colspan="1">46.98 (44.00–50.18)</td><td rowspan="1" colspan="1">3.07 (2.39–3.95)</td><td rowspan="1" colspan="1">3.28 (2.54–4.25)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">4</td><td rowspan="1" colspan="1">16.49 (13.98–19.45)</td><td rowspan="1" colspan="1">1.08 (.79–1.48)</td><td rowspan="1" colspan="1">1.28 (.93–1.76)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">5</td><td rowspan="1" colspan="1">28.47 (25.78–31.43)</td><td rowspan="1" colspan="1">1.85 (1.42–2.40)</td><td rowspan="1" colspan="1">2.14 (1.63–2.80)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">6</td><td rowspan="1" colspan="1">38.72 (27.86–30.78)</td><td rowspan="1" colspan="1">2.52 (1.91–3.33)</td><td rowspan="1" colspan="1">2.60 (1.96–3.44)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">7</td><td rowspan="1" colspan="1">38.71 (33.91–44.19)</td><td rowspan="1" colspan="1">2.54 (1.83–3.52)</td><td rowspan="1" colspan="1">2.63 (1.90–3.65)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">8</td><td rowspan="1" colspan="1">32.95 (29.02–37.42)</td><td rowspan="1" colspan="1">2.17 (1.60–2.95)</td><td rowspan="1" colspan="1">2.21 (1.63–3.01)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">9</td><td rowspan="1" colspan="1">64.60 (58.58–71.24)</td><td rowspan="1" colspan="1">4.23 (3.22–5.57)</td><td rowspan="1" colspan="1">3.96 (3.00–5.22)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">10</td><td rowspan="1" colspan="1">30.38 (23.15–39.87)</td><td rowspan="1" colspan="1">2.00 (1.15–3.47)</td><td rowspan="1" colspan="1">1.99 (1.14–3.44)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">11</td><td rowspan="1" colspan="1">67.79 (54.52–84.28)</td><td rowspan="1" colspan="1">4.42 (2.72–7.18)</td><td rowspan="1" colspan="1">3.67 (2.21–6.10)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">12</td><td rowspan="1" colspan="1">57.00 (38.21–85.05)</td><td rowspan="1" colspan="1">3.63 (1.23–10.73)</td><td rowspan="1" colspan="1">1.04 (.28–3.82)</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">13</td><td rowspan="1" colspan="1">77.28 (63.46–94.11)</td><td rowspan="1" colspan="1">5.12 (3.64–7.20)</td><td rowspan="1" colspan="1">3.57 (2.46–5.17)</td><td rowspan="1" colspan="1"></td></tr></tbody></table><table-wrap-foot><fn><p>Abbreviations: CI, confidence interval; HIV, human immunodeficiency virus; HR, hazard ratio.</p></fn><fn><p><sup>a</sup> Variables adjusted for each other.</p></fn></table-wrap-foot></table-wrap></p></sec><sec id="s3c"><title>Association Between Malaria in Pregnancy and Childhood Malaria</title><p>After adjusting for maternal age, parity, education, mosquito net ownership, household socioeconomic status, maternal HIV status, and location of residence, maternal malaria was associated with a significantly higher incidence of childhood malaria (adjusted hazard ratio [aHR], 1.23; 95% CI, 1.01–1.51]; <italic>P</italic> = .04). However, the positive association observed between maternal malaria and childhood asymptomatic parasitemia did not reach statistical significance (adjusted odds ratio [aOR], 1.27; 95% CI, .83–1.97; <italic>P</italic> = .28). Infection intensity did not affect the association. The association was not modified by maternal HIV (<italic>P</italic><sub>interaction</sub> = .20) or child albendazole (<italic>P</italic> = .60).</p></sec><sec id="s3d"><title>Association Between Maternal Helminth Infections in Pregnancy and Childhood Malaria</title><p>Children of mothers with hookworm or <italic>M. perstans</italic> in pregnancy had significantly higher rates of clinical malaria and increased odds of asymptomatic parasitemia compared with children of uninfected mothers (<xref ref-type="table" rid="JIT397TB3">Tables 3</xref> and <xref ref-type="table" rid="JIT397TB4">4</xref>). Simultaneously adjusting for each helminth did not change the association between maternal hookworm and childhood clinical malaria (aHR, 1.18; 95% CI, 1.04–1.34; <italic>P</italic> = .01) or childhood asymptomatic parasitemia (aOR, 1.43; 95% CI, 1.08–1.90; <italic>P</italic> = .01) but weakened the association between maternal <italic>M. perstans</italic> and childhood clinical malaria (aHR, 1.14; 95% CI, 1.00–1.30; <italic>P</italic> = .06) or childhood asymptomatic parasitemia (aOR, 1.26; 95% CI, .92–1.74; <italic>P</italic> = .15). Overall, there was no association between maternal <italic>S. mansoni</italic> infection and childhood clinical malaria or asymptomatic parasitaemia (Tables <xref ref-type="table" rid="JIT397TB3">3</xref> and <xref ref-type="table" rid="JIT397TB4">4</xref>). Maternal HIV did not modify the associations between childhood malaria and maternal hookworm (<italic>P</italic> = .10), <italic>M. perstans</italic> (<italic>P</italic> = .80), or <italic>S. mansoni</italic> (<italic>P</italic> = .80). Similarly, child albendazole did not modify the associations between childhood malaria and maternal hookworm (<italic>P</italic> = .30), <italic>M. perstans</italic> (<italic>P</italic> = .10), or <italic>S. mansoni</italic> (<italic>P</italic> = .70).
<table-wrap id="JIT397TB3" position="float"><label>Table 3.</label><caption><p>Association Between Maternal Helminth Infections and Clinical Malaria Episodes in Childhood (aged 0–5 years)</p></caption><table frame="hsides" rules="groups"><colgroup span="1"><col align="left" span="1"></col><col align="char" char="(" span="1"></col><col align="char" char="." span="1"></col><col align="char" char="." span="1"></col><col align="char" char="." span="1"></col><col align="char" char="." span="1"></col><col align="char" char="." span="1"></col></colgroup><thead><tr><th align="left" rowspan="1" colspan="1">Maternal Infection Status</th><th align="left" rowspan="1" colspan="1">Incidence Rate per 100 Person-Years (95% CI)</th><th align="left" rowspan="1" colspan="1">Cox HR (95% CI)</th><th align="left" rowspan="1" colspan="1">Adjusted HR<sup>a</sup> (95% CI)</th><th align="left" rowspan="1" colspan="1"><italic>P</italic> Value</th><th align="left" rowspan="1" colspan="1">Adjusted HR<sup>b</sup> (95% CI)</th><th align="left" rowspan="1" colspan="1"><italic>P</italic> Value</th></tr></thead><tbody><tr><td rowspan="1" colspan="1">No hookworm</td><td rowspan="1" colspan="1">29.28 (27.86–30.78)</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">Hookworm</td><td rowspan="1" colspan="1">39.93 (38.04–41.91)</td><td rowspan="1" colspan="1">1.36 (1.20–1.54)</td><td rowspan="1" colspan="1">1.26 (1.10–1.43)</td><td rowspan="1" colspan="1"><.001</td><td rowspan="1" colspan="1">1.23 (1.09–1.40)</td><td rowspan="1" colspan="1">.001</td></tr><tr><td rowspan="1" colspan="1">No <italic>Mansonella perstans</italic></td><td rowspan="1" colspan="1">31.83 (30.58–33.15)</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"><italic>M. perstans</italic></td><td rowspan="1" colspan="1">40.75 (38.06–43.64)</td><td rowspan="1" colspan="1">1.30 (1.12–1.51)</td><td rowspan="1" colspan="1">1.24 (1.07–1.42)</td><td rowspan="1" colspan="1">.003</td><td rowspan="1" colspan="1">1.19 (1.03–1.37)</td><td rowspan="1" colspan="1">.02</td></tr><tr><td rowspan="1" colspan="1">No <italic>Schistosoma mansoni</italic></td><td rowspan="1" colspan="1">33.07 (31.81–34.38)</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"><italic>S. mansoni</italic></td><td rowspan="1" colspan="1">37.74 (34.96–40.74)</td><td rowspan="1" colspan="1">1.14 (.97–1.35)</td><td rowspan="1" colspan="1">1.07 (.91–1.26)</td><td rowspan="1" colspan="1">.43</td><td rowspan="1" colspan="1">1.06 (.90–1.25)</td><td rowspan="1" colspan="1">.48</td></tr></tbody></table><table-wrap-foot><fn><p>Abbreviations: CI, confidence interval; HR, hazard ratio.</p></fn><fn><p><sup>a</sup> Adjusted for maternal age, education, parity, net ownership, socioeconomic status, and maternal malaria and human immunodeficiency virus infections.</p></fn><fn><p><sup>b</sup> In addition adjusted for geographical zone.</p></fn></table-wrap-foot></table-wrap><table-wrap id="JIT397TB4" position="float"><label>Table 4.</label><caption><p>Association Between Maternal Helminth Infections in Pregnancy and the Prevalence of Childhood Asymptomatic Parasitemia (aged 0–5 years)</p></caption><table frame="hsides" rules="groups"><colgroup span="1"><col align="left" span="1"></col><col align="char" char="(" span="1"></col><col align="char" char="." span="1"></col><col align="char" char="." span="1"></col><col align="char" char="." span="1"></col><col align="char" char="." span="1"></col><col align="char" char="." span="1"></col></colgroup><thead><tr><th align="left" rowspan="1" colspan="1">Maternal Infection Status</th><th align="left" rowspan="1" colspan="1">No. of Children Ever Parasitemic at Any Time Point (%)</th><th align="left" rowspan="1" colspan="1">Crude OR (95% CI)</th><th align="left" rowspan="1" colspan="1">Adjusted OR<sup>a</sup> (95% CI)</th><th align="left" rowspan="1" colspan="1"><italic>P</italic> Value</th><th align="left" rowspan="1" colspan="1">Adjusted OR<sup>b</sup> (95% CI)</th><th align="left" rowspan="1" colspan="1"><italic>P</italic> Value</th></tr></thead><tbody><tr><td rowspan="1" colspan="1">No hookworm</td><td rowspan="1" colspan="1">160 (4.2)</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1">Hookworm</td><td rowspan="1" colspan="1">179 (6.6)</td><td rowspan="1" colspan="1">1.76 (1.31–2.38)</td><td rowspan="1" colspan="1">1.63 (1.22–2.17)</td><td rowspan="1" colspan="1">.001</td><td rowspan="1" colspan="1">1.57 (1.18–2.08)</td><td rowspan="1" colspan="1">.002</td></tr><tr><td rowspan="1" colspan="1">No <italic>Mansonella perstans</italic></td><td rowspan="1" colspan="1">282 (4.9)</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"><italic>M. perstans</italic></td><td rowspan="1" colspan="1">113 (7.4)</td><td rowspan="1" colspan="1">1.71 (1.24–2.35)</td><td rowspan="1" colspan="1">1.49 (1.08–2.06)</td><td rowspan="1" colspan="1">.02</td><td rowspan="1" colspan="1">1.36 (.99–1.88)</td><td rowspan="1" colspan="1">.06</td></tr><tr><td rowspan="1" colspan="1">No <italic>Schistosoma mansoni</italic></td><td rowspan="1" colspan="1">322 (5.4)</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"><italic>S. mansoni</italic></td><td rowspan="1" colspan="1">76 (5.7)</td><td rowspan="1" colspan="1">1.07 (.75–1.53)</td><td rowspan="1" colspan="1">1.00 (.69–1.44)</td><td rowspan="1" colspan="1">1.00</td><td rowspan="1" colspan="1">0.99 (.69–1.41)</td><td rowspan="1" colspan="1">.96</td></tr></tbody></table><table-wrap-foot><fn><p>Abbreviations: CI, confidence interval; OR, odds ratio.</p></fn><fn><p><sup>a</sup> Adjusted for maternal age, education, parity, net ownership, socioeconomic status, and maternal malaria and human immunodeficiency virus infection.</p></fn><fn><p><sup>b</sup> In addition adjusted for geographical zone.</p></fn></table-wrap-foot></table-wrap></p></sec><sec id="s3e"><title>Association Between Malaria–Helminth Coinfections in Pregnancy and Childhood Malaria</title><p>Associations between childhood malaria and maternal hookworm or <italic>M. perstans</italic> did not differ when stratified by maternal malaria status. An association between maternal <italic>S. mansoni</italic> and childhood parasitemia was observed only in the presence of maternal malaria (<xref ref-type="table" rid="JIT397TB5">Tables 5</xref> and <xref ref-type="table" rid="JIT397TB6">6</xref>).
<table-wrap id="JIT397TB5" position="float"><label>Table 5.</label><caption><p>Association Between Maternal Helminth Infections in Pregnancy and Childhood Clinical Malaria (aged 0–5 years), Stratified by Maternal Malaria</p></caption><table frame="hsides" rules="groups"><colgroup span="1"><col align="left" span="1"></col><col align="char" char="(" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col><col align="left" span="1"></col></colgroup><thead><tr><th align="left" rowspan="1" colspan="1">Maternal Infection Status</th><th align="left" rowspan="1" colspan="1">Incidence rate per 100 pyrs (95% CI)</th><th align="left" rowspan="1" colspan="1">Cox HR (95% CI)</th><th align="left" rowspan="1" colspan="1">Adjusted HR<sup>a</sup> (95% CI)</th><th align="left" rowspan="1" colspan="1"><italic>P</italic> Value</th><th align="left" rowspan="1" colspan="1">Adjusted HR<sup>b</sup> (95% CI)</th><th align="left" rowspan="1" colspan="1"><italic>P</italic> Value</th></tr></thead><tbody><tr><td colspan="7" rowspan="1">No malaria</td></tr><tr><td rowspan="1" colspan="1"> No hookworm</td><td rowspan="1" colspan="1">28.81 (27.33,30.38)</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"> Hookworm</td><td rowspan="1" colspan="1">37.93 (35.95,40.01)</td><td rowspan="1" colspan="1">1.31 (1.15–1.50)</td><td rowspan="1" colspan="1">1.20 (1.05–1.38)</td><td rowspan="1" colspan="1">.01</td><td rowspan="1" colspan="1">1.17 (1.03–1.34)</td><td rowspan="1" colspan="1">.02</td></tr><tr><td colspan="7" rowspan="1">Had malaria</td></tr><tr><td rowspan="1" colspan="1"> No hookworm</td><td rowspan="1" colspan="1">35.09 (29.96,41.09)</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"> Hookworm</td><td rowspan="1" colspan="1">52.46 (46.48,59.21)</td><td rowspan="1" colspan="1">1.48 (1.03–2.14)</td><td rowspan="1" colspan="1">1.63 (1.15–2.32)</td><td rowspan="1" colspan="1">.01</td><td rowspan="1" colspan="1">1.60 (1.13–2.26)</td><td rowspan="1" colspan="1">.01</td></tr><tr><td colspan="7" rowspan="1"><italic>P</italic><sub>interaction</sub> = .23<sup>c</sup></td></tr><tr><td colspan="7" rowspan="1">No malaria</td></tr><tr><td rowspan="1" colspan="1"> No <italic>Mansonella perstans</italic></td><td rowspan="1" colspan="1">30.79 (29.49,32.15)</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"> <italic>M. perstans</italic></td><td rowspan="1" colspan="1">40.05 (37.13,43.21)</td><td rowspan="1" colspan="1">1.30 (1.12–1.51)</td><td rowspan="1" colspan="1">1.26 (1.08–1.46)</td><td rowspan="1" colspan="1">.003</td><td rowspan="1" colspan="1">1.21 (1.03–1.40)</td><td rowspan="1" colspan="1">.02</td></tr><tr><td colspan="7" rowspan="1">Had malaria</td></tr><tr><td rowspan="1" colspan="1"> No <italic>M. perstans</italic></td><td rowspan="1" colspan="1">44.33 (39.35,49.93)</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"> <italic>M. perstans</italic></td><td rowspan="1" colspan="1">44.34 (37.68,52.18)</td><td rowspan="1" colspan="1">0.99 (.70–1.40)</td><td rowspan="1" colspan="1">1.25 (.87–1.79)</td><td rowspan="1" colspan="1">.23</td><td rowspan="1" colspan="1">1.22 (.85–1.76)</td><td rowspan="1" colspan="1">.28</td></tr><tr><td colspan="7" rowspan="1"><italic>P</italic><sub>interaction</sub> = .32<sup>c</sup></td></tr><tr><td colspan="7" rowspan="1">No malaria</td></tr><tr><td rowspan="1" colspan="1"> No <italic>Schistosoma mansoni</italic></td><td rowspan="1" colspan="1">31.85 (30.53,33.22)</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"> <italic>S. mansoni</italic></td><td rowspan="1" colspan="1">36.41 (33.52,39,54)</td><td rowspan="1" colspan="1">1.14 (.96–1.36)</td><td rowspan="1" colspan="1">1.10 (.92–1.31)</td><td rowspan="1" colspan="1">.29</td><td rowspan="1" colspan="1">1.09 (.92–1.29)</td><td rowspan="1" colspan="1">.33</td></tr><tr><td colspan="7" rowspan="1">Had malaria</td></tr><tr><td rowspan="1" colspan="1"> No <italic>S. mansoni</italic></td><td rowspan="1" colspan="1">43.91 (39.49,48.83)</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"> <italic>S. mansoni</italic></td><td rowspan="1" colspan="1">46.36 (36.97,58.14)</td><td rowspan="1" colspan="1">1.06 (.61–1.86)</td><td rowspan="1" colspan="1">0.86 (.53–1.41)</td><td rowspan="1" colspan="1">.56</td><td rowspan="1" colspan="1">0.88 (.53–1.44)</td><td rowspan="1" colspan="1">.60</td></tr><tr><td colspan="7" rowspan="1"><italic>P</italic><sub>interaction</sub> = .50<sup>c</sup></td></tr></tbody></table><table-wrap-foot><fn><p>Abbreviations: CI, confidence interval; HR, hazard ratio.</p></fn><fn><p><sup>a</sup> Adjusted for maternal age, education, parity, net ownership, socioeconomic status, and maternal human immunodeficiency virus infection.</p></fn><fn><p><sup>b</sup> In addition adjusted for geographical zone.</p></fn><fn><p><sup>c</sup> Interaction test corresponding to the model adjusted for geographical zone.</p></fn></table-wrap-foot></table-wrap><table-wrap id="JIT397TB6" position="float"><label>Table 6.</label><caption><p>Association Between Maternal Helminth Infections in Pregnancy and the Prevalence of Childhood Asymptomatic Parasitemia (aged 0–5 years), Stratified by Maternal Malaria</p></caption><table frame="hsides" rules="groups"><colgroup span="1"><col align="left" span="1"></col><col align="char" char="(" span="1"></col><col align="char" char="." span="1"></col><col align="char" char="." span="1"></col><col align="char" char="." span="1"></col><col align="char" char="." span="1"></col><col align="char" char="." span="1"></col></colgroup><thead><tr><th align="left" rowspan="1" colspan="1">Maternal Infection Status</th><th align="left" rowspan="1" colspan="1">No. of Children Ever Parasitemic at Any Time Point (%)</th><th align="left" rowspan="1" colspan="1">Crude OR (95% CI)</th><th align="left" rowspan="1" colspan="1">Adjusted OR<sup>b</sup> (95% CI)</th><th align="left" rowspan="1" colspan="1"><italic>P</italic> Value</th><th align="left" rowspan="1" colspan="1">Adjusted OR<sup>c</sup> (95% CI)</th><th align="left" rowspan="1" colspan="1"><italic>P</italic> Value</th></tr></thead><tbody><tr><td colspan="7" rowspan="1">No malaria</td></tr><tr><td rowspan="1" colspan="1"> No hookworm</td><td rowspan="1" colspan="1">160 (4.2)</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"> Hookworm</td><td rowspan="1" colspan="1">179 (6.6)</td><td rowspan="1" colspan="1">1.76 (1.31–2.38)</td><td rowspan="1" colspan="1">1.48 (1.09–2.00)</td><td rowspan="1" colspan="1">.01</td><td rowspan="1" colspan="1">1.41 (1.05–1.90)</td><td rowspan="1" colspan="1">.02</td></tr><tr><td colspan="7" rowspan="1">Had malaria</td></tr><tr><td rowspan="1" colspan="1"> No hookworm</td><td rowspan="1" colspan="1">15 (4.5)</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"> Hookworm</td><td rowspan="1" colspan="1">38 (10.4)</td><td rowspan="1" colspan="1">2.70 (1.14–6.44)</td><td rowspan="1" colspan="1">3.38 (1.33–8.63)</td><td rowspan="1" colspan="1">.01</td><td rowspan="1" colspan="1">3.29 (1.30–8.34)</td><td rowspan="1" colspan="1">.01</td></tr><tr><td colspan="7" rowspan="1"><italic>P</italic><sub>interaction</sub> = .11<sup>a</sup></td></tr><tr><td colspan="7" rowspan="1">No malaria</td></tr><tr><td rowspan="1" colspan="1"> No <italic>Mansonella perstans</italic></td><td rowspan="1" colspan="1">249 (4.7)</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"> <italic>M. perstans</italic></td><td rowspan="1" colspan="1">90 (7.0)</td><td rowspan="1" colspan="1">1.63 (1.15–2.31)</td><td rowspan="1" colspan="1">1.44 (1.02–2.04)</td><td rowspan="1" colspan="1">.04</td><td rowspan="1" colspan="1">1.31 (.93–1.84)</td><td rowspan="1" colspan="1">.12</td></tr><tr><td colspan="7" rowspan="1">Had malaria</td></tr><tr><td rowspan="1" colspan="1"> No <italic>M. perstans</italic></td><td rowspan="1" colspan="1">31 (6.7)</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"> <italic>M. perstans</italic></td><td rowspan="1" colspan="1">22 (9.3)</td><td rowspan="1" colspan="1">1.62 (.67–3.90)</td><td rowspan="1" colspan="1">2.17 (.80–5.88)</td><td rowspan="1" colspan="1">.13</td><td rowspan="1" colspan="1">2.09 (.78–5.65)</td><td rowspan="1" colspan="1">.15</td></tr><tr><td colspan="7" rowspan="1"><italic>P</italic><sub>interaction</sub> = .77<sup>a</sup></td></tr><tr><td colspan="7" rowspan="1">No malaria</td></tr><tr><td rowspan="1" colspan="1"> No <italic>Schistosoma mansoni</italic></td><td rowspan="1" colspan="1">279 (5.3)</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"> <italic>S. mansoni</italic></td><td rowspan="1" colspan="1">60 (5.0)</td><td rowspan="1" colspan="1">0.95 (.64–1.40)</td><td rowspan="1" colspan="1">0.85 (.57–1.26)</td><td rowspan="1" colspan="1">.42</td><td rowspan="1" colspan="1">0.84 (.57–1.23)</td><td rowspan="1" colspan="1">.36</td></tr><tr><td colspan="7" rowspan="1">Had malaria</td></tr><tr><td rowspan="1" colspan="1"> No <italic>S. mansoni</italic></td><td rowspan="1" colspan="1">37 (6.3)</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1">1</td><td rowspan="1" colspan="1"></td></tr><tr><td rowspan="1" colspan="1"> <italic>S. mansoni</italic></td><td rowspan="1" colspan="1">16 (14.2)</td><td rowspan="1" colspan="1">2.98 (1.08–8.24)</td><td rowspan="1" colspan="1">3.12 (1.05–9.27)</td><td rowspan="1" colspan="1">.04</td><td rowspan="1" colspan="1">3.15 (1.06–9.39)</td><td rowspan="1" colspan="1">.04</td></tr><tr><td colspan="7" rowspan="1"><italic>P</italic><sub>interaction</sub> = .02<sup>a</sup></td></tr></tbody></table><table-wrap-foot><fn><p>Abbreviations: CI, confidence interval; OR, odds ratio.</p></fn><fn><p><sup>a</sup> Interaction test corresponding to the model adjusted for geographical zone.</p></fn><fn><p><sup>b</sup> Adjusted for maternal age, education, parity, net ownership, socioeconomic status, and maternal human immunodeficiency virus infection.</p></fn><fn><p><sup>c</sup> In addition adjusted for geographical zone.</p></fn></table-wrap-foot></table-wrap></p></sec></sec><sec sec-type="discussion" id="s4"><title>DISCUSSION</title><p>To our knowledge, this is the first report of a birth cohort showing an association between helminth infections in pregnancy and childhood malaria. Earlier studies exploring the influence of helminth infections on the course of malaria and the effect of malaria–helminth coinfections [<xref ref-type="bibr" rid="JIT397C18">18</xref>, <xref ref-type="bibr" rid="JIT397C38">38</xref>–<xref ref-type="bibr" rid="JIT397C41">41</xref>] used different study designs and showed both beneficial and detrimental association [<xref ref-type="bibr" rid="JIT397C36">36</xref>].</p><p>Our main finding was higher malaria morbidity (both in terms of clinical episodes and of asymptomatic parasitemia) among children of mothers with hookworm and <italic>M. perstans</italic> infections in pregnancy compared with children of uninfected mothers.</p><p>Additionally we observed an increased rate of childhood clinical malaria in children of mothers with malaria compared with children of mothers without malaria. Whereas other studies have described associations between placental malaria infection and childhood malaria [<xref ref-type="bibr" rid="JIT397C8">8</xref>, <xref ref-type="bibr" rid="JIT397C9">9</xref>, <xref ref-type="bibr" rid="JIT397C42">42</xref>, <xref ref-type="bibr" rid="JIT397C43">43</xref>], we report associations with maternal peripheral parasitemia.</p><p>At enrolment, pregnant women with hookworm and <italic>M. perstans</italic> infections were at increased risk of peripheral malaria parasitemia [<xref ref-type="bibr" rid="JIT397C16">16</xref>], suggesting that the association we observed between the maternal helminth infections and childhood malaria might be explained by the association with malaria in pregnancy. However, in the analyses stratified by maternal malaria status, maternal hookworm infection was associated with an increased rate of childhood clinical malaria and an increased prevalence of childhood parasitemia, irrespective of whether the mother had malaria or not. Also, the association between maternal hookworm and childhood malaria remained consistent after simultaneously adjusting for each helminth, whereas the adjustment weakened the association between maternal <italic>M. perstans</italic> and childhood malaria. This suggests that the association between maternal hookworm and childhood malaria may be independent of the association with maternal malaria and the other helminth infections.</p><p>A possible explanation for these findings is that mothers with helminths and malaria in pregnancy came from a high malaria transmission environment and that the child's increased malaria risk was partly due to this. The risk of maternal malaria varied significantly by geographical zone of residence [<xref ref-type="bibr" rid="JIT397C16">16</xref>], suggesting that children of women living in high malaria transmission areas would be more exposed than children of mothers living in areas with lower transmission. Nevertheless, the association between maternal malaria, hookworm, and <italic>M. perstans</italic> and childhood malaria persisted after adjusting for location of residence. However, we were unable to accurately assess the contribution of malaria transmission in the observed associations because we did not measure malaria exposure at the household or individual level. In the multivariable analyses, we adjusted for geographical location of residence assuming homogenous malaria transmission zones within an area of 4 km in diameter, which may not be sensitive to within-area transmission variations, and therefore we cannot exclude a role for malaria transmission in the observed associations.</p><p>Previous studies have reported greater malaria morbidity associated with <italic>S. mansoni</italic> coinfection [<xref ref-type="bibr" rid="JIT397C44">44</xref>]. In our study, maternal schistosome infections were mostly light to moderate, and only 2% (37 of 2237) of the mothers had malaria–<italic>S. mansoni</italic> coinfection, but we observed that children of <italic>S. mansoni–</italic>infected mothers were at higher risk of malaria parasitemia only if the mother also had malaria. This result should be interpreted with caution because it is not consistent with the association between clinical malaria and maternal <italic>S. mansoni,</italic> and we cannot rule out that this finding was due to chance alone. However, the result suggests the hypothesis that exposure to both malaria and helminths is required to alter the way the fetus's initial response to malaria is primed. In fact this may also be the case for the malaria–hookworm interaction. Although the associations between maternal hookworm and childhood malaria were statistically similar between children of mothers with and without malaria, the point estimates were lower in the strata of mothers without malaria. There may have been some misclassification of maternal malaria and, if exposure of the fetus to both malaria and hookworm is required for the observed effects, the observed trend in hazard ratios could have occurred if about 20% of the “no malaria” mothers actually had malaria at some time during the pregnancy. This would explain the absence of interaction between maternal malaria and hookworm or <italic>M. perstans</italic>.</p><p>A possible immunological explanation for the observed results is that fetal exposure to maternal helminth and malaria infections may induce T-cell hyporesponsiveness, downmodulating immunity to helminths [<xref ref-type="bibr" rid="JIT397C24">24</xref>] and malaria antigens and modifying fetal acquisition of immunity to malaria [<xref ref-type="bibr" rid="JIT397C9">9</xref>, <xref ref-type="bibr" rid="JIT397C21">21</xref>, <xref ref-type="bibr" rid="JIT397C45">45</xref>]. Tolerance in offspring exposed to parasite antigens in utero [<xref ref-type="bibr" rid="JIT397C46">46</xref>], resulting in increased susceptibility to infection, has been reported. Alternatively, coexposure to helminths and malaria might bias the profile of the antimalarial response toward a T-helper 2 profile or regulatory profile [<xref ref-type="bibr" rid="JIT397C24">24</xref>]. Another explanation is that individuals susceptible to helminths are more susceptible to malaria. Studies on helminth infections have shown that only a minority of individuals account for the majority of infection burden [<xref ref-type="bibr" rid="JIT397C47">47</xref>]. This might be due to variation in parasite exposure but could also be due to variation in individual genetic susceptibility [<xref ref-type="bibr" rid="JIT397C48">48</xref>]. Studies have suggested genetic susceptibility to polyparasitism [<xref ref-type="bibr" rid="JIT397C49">49</xref>]; hence pregnant women with a genetic susceptibility to hookworm or <italic>M. perstans</italic> infection might be more susceptible to malaria infection. However, adjusting for maternal malaria did not alter the associations between maternal hookworm or <italic>M. perstans</italic> infections and childhood malaria, suggesting that these helminth infections are not simply a marker for genetic susceptibility to malaria.</p><p>We used data collected from the EMaBS, a trial that investigated whether anthelminthic treatment during pregnancy could alter the effects of prenatal helminth exposure. Anthelminthic treatment in pregnancy was effective [<xref ref-type="bibr" rid="JIT397C14">14</xref>], but albendazole and praziquantel had no effect on childhood malaria overall or in subgroup analyses by maternal hookworm and <italic>S. mansoni</italic> infections [<xref ref-type="bibr" rid="JIT397C35">35</xref>]. This could imply that the association between maternal hookworm and childhood malaria was established early in pregnancy and that single-dose albendazole or praziquantel in the second or third trimester was not sufficient to eliminate or reverse any effect of helminth infection in pregnancy on malaria susceptibility in the offspring. This is particularly likely to be true because this analysis was based on assessment of maternal helminth and malaria status at enrollment to the study, before the trial intervention and intermittent presumptive treatment for malaria were provided to the women (>90% of the mothers received intermittent presumptive treatment for malaria in the second and/or third trimesters, greatly reducing maternal malaria prevalence). It is likely that most of the fetal exposure to maternal malaria occurred before the anthelminthic trial intervention. In contrast, childhood quarterly albendazole was associated with a 15% reduction in the incidence of clinical malaria [<xref ref-type="bibr" rid="JIT397C35">35</xref>].</p><p>Our major limitation was the use of single samples for ascertainment of maternal malaria and helminth infections. Although microscopy is the gold standard in malaria diagnosis, sensitivity is low in pregnancy due to low parasite densities and placental sequestration. In a review [<xref ref-type="bibr" rid="JIT397C50">50</xref>], the pooled prevalence estimate for peripheral malaria in East and Southern Africa was 32.0% (95% CI 25.9–38.0; n = 11 688), considerably higher than the prevalence we observed. Misclassification of malaria-infected mothers classified as malaria-negative would weaken the strength of observed associations between maternal and childhood malaria. Similarly, for helminths, some mothers may have been misclassified as uninfected. The underestimation of these key exposures may also account for the lack of interaction between maternal malaria and helminths as discussed above. Lastly, we cannot exclude the possibility that confounding by unmeasured covariables could explain some of the observations. Nonetheless, this study had the unique advantage of a prospective birth cohort design, with a large sample size, a long follow-up period, and comprehensive data on potential confounders minimizing residual confounding.</p><p>This study provides the first report of an association between helminth infections in pregnancy and malaria in the offspring and suggests that helminth infections in pregnancy may increase the overall burden of childhood malaria in regions of coendemicity. The association between maternal hookworm and childhood malaria was consistent for clinical malaria episodes and asymptomatic parasitemia. However, the mechanism is unclear, and studies are needed to elucidate the significance of maternal helminth infections on fetal and early childhood antimalarial responses. Our findings support the strategy of integrated malaria–helminth control to accelerate the reduction of malaria morbidity and provide pertinent knowledge for the evaluation of malaria vaccine trials because results might be modified by concurrent helminth infections in pregnancy.</p></sec><sec sec-type="supplementary-material" id="s5"><title>Supplementary Data</title><p><ext-link ext-link-type="uri" xlink:href="http://jid.oxfordjournals.org/lookup/suppl/doi:10.1093/infdis/jit397/-/DC1">Supplementary materials</ext-link> are available at <italic>The Journal of Infectious Diseases</italic> online (http://jid.oxfordjournals.org/). Supplementary materials consist of data provided by the author that are published to benefit the reader. The posted materials are not copyedited. The contents of all supplementary data are the sole responsibility of the authors. Questions or messages regarding errors should be addressed to the author.</p><supplementary-material id="PMC_1" content-type="local-data"><caption><title>Supplementary Data</title></caption><media mimetype="text" mime-subtype="html" xlink:href="supp_208_12_2007__index.html"></media><media xlink:role="associated-file" mimetype="application" mime-subtype="msword" xlink:href="supp_jit397_jit397supp.docx"></media><media xlink:role="associated-file" mimetype="application" mime-subtype="msword" xlink:href="supp_jit397_jit397supp_fig.docx"></media></supplementary-material></sec></body><back><ack><title>Notes</title><p><bold><italic>Acknowledgements.</italic></bold> We thank all staff and participants of the EMaB Study, the fields team in Entebbe and Katabi, and the staff of Entebbe hospital and MRC/UVRI Uganda Research Unit on AIDS. We thank Barbara Willey for her statistical advice.</p><p><bold><italic>Financial support.</italic></bold> The Entebbe Mother and Baby Study is supported by <funding-source>the Wellcome Trust</funding-source> (grant numbers <award-id>064693, 079110, 95778</award-id>) with additional funding from <funding-source>the European Community's Seventh Framework Programme</funding-source> (<award-id>FP7/2007–2013</award-id>) under EC-GA number <award-id>241642</award-id>. J. N. was supported in part by a PhD fellowship from <funding-source>the Malaria Capacity Development Consortium</funding-source> which is funded by <funding-source>Wellcome Trust</funding-source> (grant number <award-id>WT084289MA</award-id>).</p><p><bold><italic>Potential conflict of interest.</italic></bold> All other authors report no potential conflicts.</p><p>All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.</p></ack><ref-list><title>References</title><ref id="JIT397C1"><label>1</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Brooker</surname><given-names>S</given-names></name><name><surname>Akhwale</surname><given-names>W</given-names></name><name><surname>Pullan</surname><given-names>R</given-names></name><etal></etal></person-group><article-title>Epidemiology of plasmodium-helminth co-infection in Africa: populations at risk, potential impact on anemia, and prospects for combining control</article-title><source>Am J Trop Med Hyg</source><year>2007</year><volume>77</volume><fpage>88</fpage><lpage>98</lpage><pub-id pub-id-type="pmid">18165479</pub-id></element-citation></ref><ref id="JIT397C2"><label>2</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mazigo</surname><given-names>HD</given-names></name><name><surname>Waihenya</surname><given-names>R</given-names></name><name><surname>Lwambo</surname><given-names>NJ</given-names></name><etal></etal></person-group><article-title>Co-infections with <italic>Plasmodium falciparum</italic>, <italic>Schistosoma mansoni</italic> and intestinal helminths among schoolchildren in endemic areas of northwestern Tanzania</article-title><source>Parasit Vectors</source><year>2010</year><volume>3</volume><fpage>44</fpage><pub-id pub-id-type="pmid">20482866</pub-id></element-citation></ref><ref id="JIT397C3"><label>3</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mwangi</surname><given-names>TW</given-names></name><name><surname>Bethony</surname><given-names>JM</given-names></name><name><surname>Brooker</surname><given-names>S</given-names></name></person-group><article-title>Malaria and helminth interactions in humans: an epidemiological viewpoint</article-title><source>Ann Trop Med Parasitol</source><year>2006</year><volume>100</volume><fpage>551</fpage><lpage>70</lpage><pub-id pub-id-type="pmid">16989681</pub-id></element-citation></ref><ref id="JIT397C4"><label>4</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>de Silva</surname><given-names>NR</given-names></name><name><surname>Brooker</surname><given-names>S</given-names></name><name><surname>Hotez</surname><given-names>PJ</given-names></name><name><surname>Montresor</surname><given-names>A</given-names></name><name><surname>Engels</surname><given-names>D</given-names></name><name><surname>Savioli</surname><given-names>L</given-names></name></person-group><article-title>Soil-transmitted helminth infections: updating the global picture</article-title><source>Trends Parasitol</source><year>2003</year><volume>19</volume><fpage>547</fpage><lpage>51</lpage><pub-id pub-id-type="pmid">14642761</pub-id></element-citation></ref><ref id="JIT397C5"><label>5</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Snow</surname><given-names>RW</given-names></name><name><surname>Guerra</surname><given-names>CA</given-names></name><name><surname>Noor</surname><given-names>AM</given-names></name><name><surname>Myint</surname><given-names>HY</given-names></name><name><surname>Hay</surname><given-names>SI</given-names></name></person-group><article-title>The global distribution of clinical episodes of <italic>Plasmodium falciparum</italic> malaria</article-title><source>Nature</source><year>2005</year><volume>434</volume><fpage>214</fpage><lpage>7</lpage><pub-id pub-id-type="pmid">15759000</pub-id></element-citation></ref><ref id="JIT397C6"><label>6</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Desai</surname><given-names>M</given-names></name><name><surname>ter Kuile</surname><given-names>FO</given-names></name><name><surname>Nosten</surname><given-names>F</given-names></name><etal></etal></person-group><article-title>Epidemiology and burden of malaria in pregnancy</article-title><source>Lancet Infect Dis</source><year>2007</year><volume>7</volume><fpage>93</fpage><lpage>104</lpage><pub-id pub-id-type="pmid">17251080</pub-id></element-citation></ref><ref id="JIT397C7"><label>7</label><element-citation publication-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><pub-id pub-id-type="pmid">11425175</pub-id></element-citation></ref><ref id="JIT397C8"><label>8</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Le Hesran</surname><given-names>JY</given-names></name><name><surname>Cot</surname><given-names>M</given-names></name><name><surname>Personne</surname><given-names>P</given-names></name><etal></etal></person-group><article-title>Maternal placental infection with <italic>Plasmodium falciparum</italic> and malaria morbidity during the first 2 years of life</article-title><source>Am J Epidemiol</source><year>1997</year><volume>146</volume><fpage>826</fpage><lpage>31</lpage><pub-id pub-id-type="pmid">9384203</pub-id></element-citation></ref><ref id="JIT397C9"><label>9</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Malhotra</surname><given-names>I</given-names></name><name><surname>Dent</surname><given-names>A</given-names></name><name><surname>Mungai</surname><given-names>P</given-names></name><etal></etal></person-group><article-title>Can prenatal malaria exposure produce an immune tolerant phenotype? A prospective birth cohort study in Kenya</article-title><source>PLoS Med</source><year>2009</year><volume>6</volume><fpage>e1000116</fpage><pub-id pub-id-type="pmid">19636353</pub-id></element-citation></ref><ref id="JIT397C10"><label>10</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bundy</surname><given-names>DA</given-names></name><name><surname>Chan</surname><given-names>MS</given-names></name><name><surname>Savioli</surname><given-names>L</given-names></name></person-group><article-title>Hookworm infection in pregnancy</article-title><source>Trans R Soc Trop Med Hyg</source><year>1995</year><volume>89</volume><fpage>521</fpage><lpage>2</lpage><pub-id pub-id-type="pmid">8560530</pub-id></element-citation></ref><ref id="JIT397C11"><label>11</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Christian</surname><given-names>P</given-names></name><name><surname>Khatry</surname><given-names>SK</given-names></name><name><surname>West</surname><given-names>KP</given-names><suffix>Jr</suffix></name></person-group><article-title>Antenatal anthelmintic treatment, birthweight, and infant survival in rural Nepal</article-title><source>Lancet</source><year>2004</year><volume>364</volume><fpage>981</fpage><lpage>3</lpage><pub-id pub-id-type="pmid">15364190</pub-id></element-citation></ref><ref id="JIT397C12"><label>12</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Friedman</surname><given-names>JF</given-names></name><name><surname>Mital</surname><given-names>P</given-names></name><name><surname>Kanzaria</surname><given-names>HK</given-names></name><name><surname>Olds</surname><given-names>GR</given-names></name><name><surname>Kurtis</surname><given-names>JD</given-names></name></person-group><article-title>Schistosomiasis and pregnancy</article-title><source>Trends Parasitol</source><year>2007</year><volume>23</volume><fpage>159</fpage><lpage>64</lpage><pub-id pub-id-type="pmid">17336160</pub-id></element-citation></ref><ref id="JIT397C13"><label>13</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Muhangi</surname><given-names>L</given-names></name><name><surname>Woodburn</surname><given-names>P</given-names></name><name><surname>Omara</surname><given-names>M</given-names></name><etal></etal></person-group><article-title>Associations between mild-to-moderate anaemia in pregnancy and helminth, malaria and HIV infection in Entebbe, Uganda</article-title><source>Trans R Soc Trop Med Hyg</source><year>2007</year><volume>101</volume><fpage>899</fpage><lpage>907</lpage><pub-id pub-id-type="pmid">17555783</pub-id></element-citation></ref><ref id="JIT397C14"><label>14</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ndibazza</surname><given-names>J</given-names></name><name><surname>Muhangi</surname><given-names>L</given-names></name><name><surname>Akishule</surname><given-names>D</given-names></name><etal></etal></person-group><article-title>Effects of deworming during pregnancy on maternal and perinatal outcomes in Entebbe, Uganda: a randomized controlled trial</article-title><source>Clin Infect Dis</source><year>2010</year><volume>50</volume><fpage>531</fpage><lpage>40</lpage><pub-id pub-id-type="pmid">20067426</pub-id></element-citation></ref><ref id="JIT397C15"><label>15</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Adegnika</surname><given-names>AA</given-names></name><name><surname>Ramharter</surname><given-names>M</given-names></name><name><surname>Agnandji</surname><given-names>ST</given-names></name><etal></etal></person-group><article-title>Epidemiology of parasitic co-infections during pregnancy in Lambarene, Gabon</article-title><source>Trop Med Int Health</source><year>2010</year><volume>15</volume><fpage>1204</fpage><lpage>9</lpage><pub-id pub-id-type="pmid">20636299</pub-id></element-citation></ref><ref id="JIT397C16"><label>16</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hillier</surname><given-names>SD</given-names></name><name><surname>Booth</surname><given-names>M</given-names></name><name><surname>Muhangi</surname><given-names>L</given-names></name><etal></etal></person-group><article-title><italic>Plasmodium falciparum</italic> and helminth coinfection in a semi urban population of pregnant women in Uganda</article-title><source>J Infect Dis</source><year>2008</year><volume>198</volume><fpage>920</fpage><lpage>7</lpage><pub-id pub-id-type="pmid">18721060</pub-id></element-citation></ref><ref id="JIT397C17"><label>17</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Briand</surname><given-names>V</given-names></name><name><surname>Watier</surname><given-names>L</given-names></name><name><surname>JY</surname><given-names>LEH</given-names></name><name><surname>Garcia</surname><given-names>A</given-names></name><name><surname>Cot</surname><given-names>M</given-names></name></person-group><article-title>Coinfection with <italic>Plasmodium falciparum</italic> and <italic>Schistosoma haematobium</italic>: protective effect of schistosomiasis on malaria in Senegalese children?</article-title><source>Am J Trop Med Hyg</source><year>2005</year><volume>72</volume><fpage>702</fpage><lpage>7</lpage><pub-id pub-id-type="pmid">15964953</pub-id></element-citation></ref><ref id="JIT397C18"><label>18</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Spiegel</surname><given-names>A</given-names></name><name><surname>Tall</surname><given-names>A</given-names></name><name><surname>Raphenon</surname><given-names>G</given-names></name><name><surname>Trape</surname><given-names>JF</given-names></name><name><surname>Druilhe</surname><given-names>P</given-names></name></person-group><article-title>Increased frequency of malaria attacks in subjects co-infected by intestinal worms and <italic>Plasmodium falciparum</italic> malaria</article-title><source>Trans R Soc Trop Med Hyg</source><year>2003</year><volume>97</volume><fpage>198</fpage><lpage>9</lpage><pub-id pub-id-type="pmid">14584377</pub-id></element-citation></ref><ref id="JIT397C19"><label>19</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Boel</surname><given-names>M</given-names></name><name><surname>Carrara</surname><given-names>VI</given-names></name><name><surname>Rijken</surname><given-names>M</given-names></name><etal></etal></person-group><article-title>Complex interactions between soil-transmitted helminths and malaria in pregnant women on the Thai-Burmese border</article-title><source>PLoS Negl Trop Dis</source><year>2010</year><volume>4</volume><fpage>e887</fpage><pub-id pub-id-type="pmid">21103367</pub-id></element-citation></ref><ref id="JIT397C20"><label>20</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Midzi</surname><given-names>N</given-names></name><name><surname>Sangweme</surname><given-names>D</given-names></name><name><surname>Zinyowera</surname><given-names>S</given-names></name><etal></etal></person-group><article-title>The burden of polyparasitism among primary schoolchildren in rural and farming areas in Zimbabwe</article-title><source>Trans R Soc Trop Med Hyg</source><year>2008</year><volume>102</volume><fpage>1039</fpage><lpage>45</lpage><pub-id pub-id-type="pmid">18656215</pub-id></element-citation></ref><ref id="JIT397C21"><label>21</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hartgers</surname><given-names>FC</given-names></name><name><surname>Yazdanbakhsh</surname><given-names>M</given-names></name></person-group><article-title>Co-infection of helminths and malaria: modulation of the immune responses to malaria</article-title><source>Parasite Immunol</source><year>2006</year><volume>28</volume><fpage>497</fpage><lpage>506</lpage><pub-id pub-id-type="pmid">16965285</pub-id></element-citation></ref><ref id="JIT397C22"><label>22</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Maizels</surname><given-names>RM</given-names></name><name><surname>Balic</surname><given-names>A</given-names></name><name><surname>Gomez-Escobar</surname><given-names>N</given-names></name><name><surname>Nair</surname><given-names>M</given-names></name><name><surname>Taylor</surname><given-names>MD</given-names></name><name><surname>Allen</surname><given-names>JE</given-names></name></person-group><article-title>Helminth parasites—masters of regulation</article-title><source>Immunol Rev</source><year>2004</year><volume>201</volume><fpage>89</fpage><lpage>116</lpage><pub-id pub-id-type="pmid">15361235</pub-id></element-citation></ref><ref id="JIT397C23"><label>23</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Su</surname><given-names>Z</given-names></name><name><surname>Segura</surname><given-names>M</given-names></name><name><surname>Morgan</surname><given-names>K</given-names></name><name><surname>Loredo-Osti</surname><given-names>JC</given-names></name><name><surname>Stevenson</surname><given-names>MM</given-names></name></person-group><article-title>Impairment of protective immunity to blood-stage malaria by concurrent nematode infection</article-title><source>Infect Immun</source><year>2005</year><volume>73</volume><fpage>3531</fpage><lpage>9</lpage><pub-id pub-id-type="pmid">15908382</pub-id></element-citation></ref><ref id="JIT397C24"><label>24</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>van Riet</surname><given-names>E</given-names></name><name><surname>Hartgers</surname><given-names>FC</given-names></name><name><surname>Yazdanbakhsh</surname><given-names>M</given-names></name></person-group><article-title>Chronic helminth infections induce immunomodulation: consequences and mechanisms</article-title><source>Immunobiology</source><year>2007</year><volume>212</volume><fpage>475</fpage><lpage>90</lpage><pub-id pub-id-type="pmid">17544832</pub-id></element-citation></ref><ref id="JIT397C25"><label>25</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hewitson</surname><given-names>JP</given-names></name><name><surname>Grainger</surname><given-names>JR</given-names></name><name><surname>Maizels</surname><given-names>RM</given-names></name></person-group><article-title>Helminth immunoregulation: the role of parasite secreted proteins in modulating host immunity</article-title><source>Mol Biochem Parasitol</source><year>2009</year><volume>167</volume><fpage>1</fpage><lpage>11</lpage><pub-id pub-id-type="pmid">19406170</pub-id></element-citation></ref><ref id="JIT397C26"><label>26</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Helmby</surname><given-names>H</given-names></name><name><surname>Kullberg</surname><given-names>M</given-names></name><name><surname>Troye-Blomberg</surname><given-names>M</given-names></name></person-group><article-title>Altered immune responses in mice with concomitant <italic>Schistosoma mansoni</italic> and <italic>Plasmodium chabaudi</italic> infections</article-title><source>Infect Immun</source><year>1998</year><volume>66</volume><fpage>5167</fpage><lpage>74</lpage><pub-id pub-id-type="pmid">9784518</pub-id></element-citation></ref><ref id="JIT397C27"><label>27</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Novato-Silva</surname><given-names>E</given-names></name><name><surname>Gazzinelli</surname><given-names>G</given-names></name><name><surname>Colley</surname><given-names>DG</given-names></name></person-group><article-title>Immune responses during human <italic>Schistosomiasis mansoni</italic>. XVIII. Immunologic status of pregnant women and their neonates</article-title><source>Scand J Immunol</source><year>1992</year><volume>35</volume><fpage>429</fpage><lpage>37</lpage><pub-id pub-id-type="pmid">1557613</pub-id></element-citation></ref><ref id="JIT397C28"><label>28</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Druilhe</surname><given-names>P</given-names></name><name><surname>Tall</surname><given-names>A</given-names></name><name><surname>Sokhna</surname><given-names>C</given-names></name></person-group><article-title>Worms can worsen malaria: towards a new means to roll back malaria?</article-title><source>Trends Parasitol</source><year>2005</year><volume>21</volume><fpage>359</fpage><lpage>62</lpage><pub-id pub-id-type="pmid">15967721</pub-id></element-citation></ref><ref id="JIT397C29"><label>29</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Nacher</surname><given-names>M</given-names></name></person-group><article-title>Worms and malaria: resisting the temptation to generalize</article-title><source>Trends Parasitol</source><year>2006</year><volume>22</volume><fpage>350</fpage><lpage>1</lpage><comment>; author reply 1–2</comment><pub-id pub-id-type="pmid">16798090</pub-id></element-citation></ref><ref id="JIT397C30"><label>30</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Elliott</surname><given-names>AM</given-names></name><name><surname>Kizza</surname><given-names>M</given-names></name><name><surname>Quigley</surname><given-names>MA</given-names></name><etal></etal></person-group><article-title>The impact of helminths on the response to immunization and on the incidence of infection and disease in childhood in Uganda: design of a randomized, double-blind, placebo-controlled, factorial trial of deworming interventions delivered in pregnancy and early childhood [ISRCTN32849447]</article-title><source>Clin Trials</source><year>2007</year><volume>4</volume><fpage>42</fpage><lpage>57</lpage><pub-id pub-id-type="pmid">17327245</pub-id></element-citation></ref><ref id="JIT397C31"><label>31</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Okello</surname><given-names>PE</given-names></name><name><surname>Van Bortel</surname><given-names>W</given-names></name><name><surname>Byaruhanga</surname><given-names>AM</given-names></name><etal></etal></person-group><article-title>Variation in malaria transmission intensity in seven sites throughout Uganda</article-title><source>Am J Trop Med Hyg</source><year>2006</year><volume>75</volume><fpage>219</fpage><lpage>25</lpage><pub-id pub-id-type="pmid">16896122</pub-id></element-citation></ref><ref id="JIT397C32"><label>32</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Melrose</surname><given-names>W</given-names></name><name><surname>Pisters</surname><given-names>P</given-names></name><name><surname>Turner</surname><given-names>P</given-names></name><etal></etal></person-group><article-title>Prevalence of filarial antigenaemia in Papua Nnew Guinea: results of surveys by the School of Public Health and Tropical Medicine, James Cook University, Townsville, Australia</article-title><source>P N G Med J</source><year>2000</year><volume>43</volume><fpage>161</fpage><lpage>5</lpage><pub-id pub-id-type="pmid">11939296</pub-id></element-citation></ref><ref id="JIT397C33"><label>33</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Katz</surname><given-names>N</given-names></name><name><surname>Chaves</surname><given-names>A</given-names></name><name><surname>Pellegrino</surname><given-names>J</given-names></name></person-group><article-title>A simple device for quantitative stool thick-smear technique in Schistosomiasis mansoni</article-title><source>Rev Inst Med Trop Sao Paulo</source><year>1972</year><volume>14</volume><fpage>397</fpage><lpage>400</lpage><pub-id pub-id-type="pmid">4675644</pub-id></element-citation></ref><ref id="JIT397C34"><label>34</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bukusuba</surname><given-names>JW</given-names></name><name><surname>Hughes</surname><given-names>P</given-names></name><name><surname>Kizza</surname><given-names>M</given-names></name><etal></etal></person-group><article-title>Screening for intestinal helminth infection in a semi-urban cohort of pregnant women in Uganda</article-title><source>Trop Doct</source><year>2004</year><volume>34</volume><fpage>27</fpage><lpage>8</lpage><pub-id pub-id-type="pmid">14959970</pub-id></element-citation></ref><ref id="JIT397C35"><label>35</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ndibazza</surname><given-names>J</given-names></name><name><surname>Mpairwe</surname><given-names>H</given-names></name><name><surname>Webb</surname><given-names>EL</given-names></name><etal></etal></person-group><article-title>Impact of anthelminthic treatment in pregnancy and childhood on immunisations, infections and eczema in childhood: a randomised controlled trial</article-title><source>PLoS One</source><year>2012</year><volume>7</volume><fpage>e50325</fpage><pub-id pub-id-type="pmid">23236367</pub-id></element-citation></ref><ref id="JIT397C36"><label>36</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Adegnika</surname><given-names>AA</given-names></name><name><surname>Kremsner</surname><given-names>PG</given-names></name></person-group><article-title>Epidemiology of malaria and helminth interaction: a review from 2001 to 2011</article-title><source>Curr Opin HIV AIDS</source><year>2012</year><volume>7</volume><fpage>221</fpage><lpage>4</lpage><pub-id pub-id-type="pmid">22418449</pub-id></element-citation></ref><ref id="JIT397C37"><label>37</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Woodburn</surname><given-names>PW</given-names></name><name><surname>Muhangi</surname><given-names>L</given-names></name><name><surname>Hillier</surname><given-names>S</given-names></name><etal></etal></person-group><article-title>Risk factors for helminth, malaria, and HIV infection in pregnancy in Entebbe, Uganda</article-title><source>PLoS Negl Trop Dis</source><year>2009</year><volume>3</volume><fpage>e473</fpage><pub-id pub-id-type="pmid">19564904</pub-id></element-citation></ref><ref id="JIT397C38"><label>38</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Brutus</surname><given-names>L</given-names></name><name><surname>Watier</surname><given-names>L</given-names></name><name><surname>Hanitrasoamampionona</surname><given-names>V</given-names></name><name><surname>Razanatsoarilala</surname><given-names>H</given-names></name><name><surname>Cot</surname><given-names>M</given-names></name></person-group><article-title>Confirmation of the protective effect of Ascaris lumbricoides on <italic>Plasmodium falciparum</italic> infection: results of a randomized trial in Madagascar</article-title><source>Am J Trop Med Hyg</source><year>2007</year><volume>77</volume><fpage>1091</fpage><lpage>5</lpage><pub-id pub-id-type="pmid">18165528</pub-id></element-citation></ref><ref id="JIT397C39"><label>39</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sokhna</surname><given-names>C</given-names></name><name><surname>Le Hesran</surname><given-names>JY</given-names></name><name><surname>Mbaye</surname><given-names>PA</given-names></name><etal></etal></person-group><article-title>Increase of malaria attacks among children presenting concomitant infection by <italic>Schistosoma mansoni</italic> in Senegal</article-title><source>Malar J</source><year>2004</year><volume>3</volume><fpage>43</fpage><pub-id pub-id-type="pmid">15544703</pub-id></element-citation></ref><ref id="JIT397C40"><label>40</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wilson</surname><given-names>S</given-names></name><name><surname>Vennervald</surname><given-names>BJ</given-names></name><name><surname>Kadzo</surname><given-names>H</given-names></name><etal></etal></person-group><article-title>Hepatosplenomegaly in Kenyan schoolchildren: exacerbation by concurrent chronic exposure to malaria <italic>and Schistosoma mansoni</italic> infection</article-title><source>Trop Med Int Health</source><year>2007</year><volume>12</volume><fpage>1442</fpage><lpage>9</lpage><pub-id pub-id-type="pmid">18076550</pub-id></element-citation></ref><ref id="JIT397C41"><label>41</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Diallo</surname><given-names>TO</given-names></name><name><surname>Remoue</surname><given-names>F</given-names></name><name><surname>Schacht</surname><given-names>AM</given-names></name><etal></etal></person-group><article-title>Schistosomiasis co-infection in humans influences inflammatory markers in uncomplicated <italic>Plasmodium falciparum</italic> malaria</article-title><source>Parasite Immunol</source><year>2004</year><volume>26</volume><fpage>365</fpage><lpage>9</lpage><pub-id pub-id-type="pmid">15679634</pub-id></element-citation></ref><ref id="JIT397C42"><label>42</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mutabingwa</surname><given-names>TK</given-names></name><name><surname>Bolla</surname><given-names>MC</given-names></name><name><surname>Li</surname><given-names>JL</given-names></name><etal></etal></person-group><article-title>Maternal malaria and gravidity interact to modify infant susceptibility to malaria</article-title><source>PLoS Med</source><year>2005</year><volume>2</volume><fpage>e407</fpage><pub-id pub-id-type="pmid">16259531</pub-id></element-citation></ref><ref id="JIT397C43"><label>43</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Schwarz</surname><given-names>NG</given-names></name><name><surname>Adegnika</surname><given-names>AA</given-names></name><name><surname>Breitling</surname><given-names>LP</given-names></name><etal></etal></person-group><article-title>Placental malaria increases malaria risk in the first 30 months of life</article-title><source>Clin Infect Dis</source><year>2008</year><volume>47</volume><fpage>1017</fpage><lpage>25</lpage><pub-id pub-id-type="pmid">18781874</pub-id></element-citation></ref><ref id="JIT397C44"><label>44</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sangweme</surname><given-names>DT</given-names></name><name><surname>Midzi</surname><given-names>N</given-names></name><name><surname>Zinyowera-Mutapuri</surname><given-names>S</given-names></name><name><surname>Mduluza</surname><given-names>T</given-names></name><name><surname>Diener-West</surname><given-names>M</given-names></name><name><surname>Kumar</surname><given-names>N</given-names></name></person-group><article-title>Impact of schistosome infection on <italic>Plasmodium falciparum</italic> Malariometric indices and immune correlates in school age children in Burma Valley, Zimbabwe</article-title><source>PLoS Negl Trop Dis</source><year>2010</year><volume>4</volume><fpage>e882</fpage><pub-id pub-id-type="pmid">21085468</pub-id></element-citation></ref><ref id="JIT397C45"><label>45</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bonner</surname><given-names>PC</given-names></name><name><surname>Zhou</surname><given-names>Z</given-names></name><name><surname>Mirel</surname><given-names>LB</given-names></name><etal></etal></person-group><article-title>Placental malaria diminishes development of antibody responses to <italic>Plasmodium falciparum</italic> epitopes in infants residing in an area of western Kenya where <italic>P. falciparum</italic> is endemic</article-title><source>Clin Diagn Lab Immunol</source><year>2005</year><volume>12</volume><fpage>375</fpage><lpage>9</lpage><pub-id pub-id-type="pmid">15753250</pub-id></element-citation></ref><ref id="JIT397C46"><label>46</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Nossal</surname><given-names>GJ</given-names></name></person-group><article-title>Cellular mechanisms of immunologic tolerance</article-title><source>Annu Rev Immunol</source><year>1983</year><volume>1</volume><fpage>33</fpage><lpage>62</lpage><pub-id pub-id-type="pmid">6399977</pub-id></element-citation></ref><ref id="JIT397C47"><label>47</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bradley</surname><given-names>DJ</given-names></name><name><surname>May</surname><given-names>RM</given-names></name></person-group><article-title>Consequences of helminth aggregation for the dynamics of schistosomiasis</article-title><source>Trans R Soc Trop Med Hyg</source><year>1978</year><volume>72</volume><fpage>262</fpage><lpage>73</lpage><pub-id pub-id-type="pmid">675786</pub-id></element-citation></ref><ref id="JIT397C48"><label>48</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Breitling</surname><given-names>LP</given-names></name><name><surname>Wilson</surname><given-names>AJ</given-names></name><name><surname>Raiko</surname><given-names>A</given-names></name><etal></etal></person-group><article-title>Heritability of human hookworm infection in Papua New Guinea</article-title><source>Parasitology</source><year>2008</year><volume>135</volume><fpage>1407</fpage><lpage>15</lpage><pub-id pub-id-type="pmid">18937884</pub-id></element-citation></ref><ref id="JIT397C49"><label>49</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ellis</surname><given-names>MK</given-names></name><name><surname>McManus</surname><given-names>DP</given-names></name></person-group><article-title>Familial aggregation of human helminth infection in the Poyang lake area of China with a focus on genetic susceptibility to schistosomiasis japonica and associated markers of disease</article-title><source>Parasitology</source><year>2009</year><volume>136</volume><fpage>699</fpage><lpage>712</lpage><pub-id pub-id-type="pmid">19486544</pub-id></element-citation></ref><ref id="JIT397C50"><label>50</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chico</surname><given-names>RM</given-names></name><name><surname>Mayaud</surname><given-names>P</given-names></name><name><surname>Ariti</surname><given-names>C</given-names></name><name><surname>Mabey</surname><given-names>D</given-names></name><name><surname>Ronsmans</surname><given-names>C</given-names></name><name><surname>Chandramohan</surname><given-names>D</given-names></name></person-group><article-title>Prevalence of malaria and sexually transmitted and reproductive tract infections in pregnancy in sub-Saharan Africa: a systematic review</article-title><source>JAMA</source><year>2012</year><volume>307</volume><fpage>2079</fpage><lpage>86</lpage><pub-id pub-id-type="pmid">22665107</pub-id></element-citation></ref></ref-list></back></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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