{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T07:27:38Z","timestamp":1791530858599,"version":"4.3.4"},"reference-count":49,"publisher":"BMJ","issue":"7","funder":[{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2018,5,4]]},"published-print":{"date-parts":[[2018,7]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>In many developing areas in the world, a high burden of enteric pathogens in early childhood are associated with growth deficits. The tryptophan-kynurenine-niacin pathway has been linked to enteric inflammatory responses to intestinal infections. However, it is not known in these settings whether scheduled antimicrobial intervention to reduce subclinical enteric pathogen carriage or repletion of the tryptophan-kynurenine-niacin pathway improves linear growth and development.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>We are conducting a randomised, placebo-controlled, factorial intervention trial in the rural setting of Haydom, Tanzania. We are recruiting 1188 children within the first 14 days of life, who will be randomised in a 2\u00d72\u2009factorial design to administration of antimicrobials (azithromycin and nitazoxanide, randomised together) and nicotinamide. The nicotinamide is administered as a daily oral dose, which for breast-feeding children aged 0\u20136 months is given to the mother and for children aged 6\u201318 months is given to the child directly. Azithromycin is given to the child as a single oral dose at months 6, 9, 12 and 15; nitazoxanide is given as a 3-day course at months 12 and 15. Mother\/child pairs are followed via monthly in-home visits. The primary outcome is the child\u2019s length-for-age Z-score at 18 months. Secondary outcomes for the child include additional anthropometry measures; stool pathogen burden and bacterial microbiome; systemic and enteric inflammation; blood metabolomics, growth factors, inflammation and nutrition; hydrogen breath assessment to estimate small-intestinal bacterial overgrowth and assessment of cognitive development. Secondary outcomes for the mother include breastmilk content of nicotinamide, other vitamins and amino acids; blood measures of tryptophan-kynurenine-niacin pathway and stool pathogens.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>This trial has been approved by the Tanzanian National Institute for Medical Research, the Tanzanian FDA and the University of Virginia IRB. Findings will be presented at national and international conferences and published in peer-review journals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Protocol version<\/jats:title>\n                    <jats:p>5.0, 4 December 2017.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Protocol sponsor<\/jats:title>\n                    <jats:p>Haydom Lutheran Hospital, Haydom, Manyara, Tanzania.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"NCT03268902\" ext-link-type=\"clintrialgov\" specific-use=\"clinicaltrial pre-results\">NCT03268902<\/jats:ext-link>\n                      ; Pre-results.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2018-021817","type":"journal-article","created":{"date-parts":[[2018,7,7]],"date-time":"2018-07-07T08:15:46Z","timestamp":1530951346000},"page":"e021817","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":23,"title":["Early Life Interventions for Childhood Growth and Development in Tanzania (ELICIT): a protocol for a randomised factorial, double-blind, placebo-controlled trial of azithromycin, nitazoxanide and nicotinamide"],"prefix":"10.1136","volume":"8","clinical-trial-number":[{"clinical-trial-number":"nct03268902","registry":"10.18810\/clinical-trials-gov","type":"preResults"},{"clinical-trial-number":"nct03268902","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Mark Daniel","family":"DeBoer","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Virginia, Charlottesville, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James A","family":"Platts-Mills","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Virginia, Charlottesville, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3381-5594","authenticated-orcid":false,"given":"Rebecca J","family":"Scharf","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Virginia, Charlottesville, Virginia, USA"},{"name":"Department of Medicine, University of Virginia, Charlottesville, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joann M","family":"McDermid","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Virginia, Charlottesville, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne W","family":"Wanjuhi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Virginia, Charlottesville, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Gratz","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Virginia, Charlottesville, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erling","family":"Svensen","sequence":"additional","affiliation":[{"name":"Department of Global Health and Primary Care, University of Bergen, Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon R","family":"Swann","sequence":"additional","affiliation":[{"name":"Department of Surgery & Cancer, Imperial College of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey R","family":"Donowitz","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease, Children\u2019s Hospital of Richmond at Virginia Commonwealth University, Richmond, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samwel","family":"Jatosh","sequence":"additional","affiliation":[{"name":"Haydom Global Health Research Centre, Haydom Lutheran Hospital, Haydom, Tanzania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric R","family":"Houpt","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Virginia, Charlottesville, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estomih","family":"Mduma","sequence":"additional","affiliation":[{"name":"Haydom Global Health Research Centre, Haydom Lutheran Hospital, Haydom, Tanzania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2018,7,7]]},"reference":[{"key":"2025121514561666000_8.7.e021817.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)60032-4"},{"key":"2025121514561666000_8.7.e021817.2","doi-asserted-by":"publisher","DOI":"10.1179\/2046905514Y.0000000158"},{"key":"2025121514561666000_8.7.e021817.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2017.02.024"},{"issue":"Suppl 4","key":"2025121514561666000_8.7.e021817.4","doi-asserted-by":"crossref","first-page":"S325","DOI":"10.1093\/cid\/ciu439","article-title":"The etiology, risk factors, and interactions of enteric infections and malnutrition and the consequences for child health and development study (MAL-ED): description of the Tanzanian site","volume":"59 Suppl 4","author":"Mduma","year":"2014","journal-title":"Clin Infect Dis"},{"key":"2025121514561666000_8.7.e021817.5","doi-asserted-by":"crossref","first-page":"e1002408","DOI":"10.1371\/journal.pmed.1002408","article-title":"Childhood stunting in relation to the pre- and postnatal environment during the first 2 years of life: The MAL-ED longitudinal birth cohort study","volume":"14","author":"MAL-ED Network Investigators","year":"2017","journal-title":"PLoS Med"},{"key":"2025121514561666000_8.7.e021817.6","doi-asserted-by":"crossref","unstructured":"Scharf RJ , Rogawski ET , Murray-Kolb LE , et al . Early childhood growth and cognitive outcomes: Findings from the MAL-ED study. Matern Child Nutr. In Press. 2018:e12584.doi:10.1111\/mcn.12584","DOI":"10.1111\/mcn.12584"},{"key":"2025121514561666000_8.7.e021817.7","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2016-2828G"},{"key":"2025121514561666000_8.7.e021817.8","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(15)00151-5"},{"key":"2025121514561666000_8.7.e021817.9","doi-asserted-by":"publisher","DOI":"10.1136\/bmjgh-2017-000370"},{"key":"2025121514561666000_8.7.e021817.10","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1093\/jpids\/piw082","article-title":"Determinants and Impact of Giardia Infection in the First 2 Years of Life in the MAL-ED Birth Cohort","volume":"6","author":"Rogawski","year":"2017","journal-title":"J Pediatric Infect Dis Soc"},{"key":"2025121514561666000_8.7.e021817.11","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.g2267"},{"key":"2025121514561666000_8.7.e021817.12","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2009.1266"},{"key":"2025121514561666000_8.7.e021817.13","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.2012.12-0284"},{"key":"2025121514561666000_8.7.e021817.14","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)11401-2"},{"key":"2025121514561666000_8.7.e021817.15","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1056\/NEJMoa1616361","article-title":"NAD Deficiency, Congenital Malformations, and Niacin Supplementation","volume":"377","author":"Shi","year":"2017","journal-title":"N Engl J Med"},{"key":"2025121514561666000_8.7.e021817.16","unstructured":"Chen C , Mitchell NJ , Gratz J , et al . Fumonisin, Not Aflatoxin, is Associated with Growth Impairment in Tanzanian Children. Environmental International. In Press. 2018."},{"key":"2025121514561666000_8.7.e021817.17","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-010-0752-7"},{"key":"2025121514561666000_8.7.e021817.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2013.08.003"},{"key":"2025121514561666000_8.7.e021817.19","doi-asserted-by":"publisher","DOI":"10.1038\/nature11228"},{"key":"2025121514561666000_8.7.e021817.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2004.05.004"},{"key":"2025121514561666000_8.7.e021817.21","doi-asserted-by":"publisher","DOI":"10.1002\/ibd.21849"},{"key":"2025121514561666000_8.7.e021817.22","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3000632"},{"key":"2025121514561666000_8.7.e021817.23","doi-asserted-by":"publisher","DOI":"10.1038\/srep19780"},{"key":"2025121514561666000_8.7.e021817.24","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.16-0037"},{"key":"2025121514561666000_8.7.e021817.25","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.114.105106"},{"key":"2025121514561666000_8.7.e021817.26","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1037\/dev0000182","article-title":"Maternal scaffolding and home stimulation: Key mediators of early intervention effects on children\u2019s cognitive development","volume":"52","author":"Obradovi\u0107","year":"2016","journal-title":"Dev Psychol"},{"key":"2025121514561666000_8.7.e021817.27","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)60555-2"},{"key":"2025121514561666000_8.7.e021817.28","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1111\/cch.12287","article-title":"The development and reliability of an observational tool for assessing mother-child interactions in field studies- experience from Pakistan","volume":"41","author":"Rasheed","year":"2015","journal-title":"Child Care Health Dev"},{"key":"2025121514561666000_8.7.e021817.29","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1000273"},{"key":"2025121514561666000_8.7.e021817.30","doi-asserted-by":"crossref","unstructured":"Bayley N . Bayley Scales of Infant and Toddler Development. San Antonio, TX: The Psychological Corporation, 2006.","DOI":"10.1037\/t14978-000"},{"key":"2025121514561666000_8.7.e021817.31","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciu437"},{"key":"2025121514561666000_8.7.e021817.32","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2014.11.001"},{"key":"2025121514561666000_8.7.e021817.33","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02102-15"},{"key":"2025121514561666000_8.7.e021817.34","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12948"},{"key":"2025121514561666000_8.7.e021817.35","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1111\/tmi.12580","article-title":"Establishment of biochemistry reference values for healthy Tanzanian infants, children and adolescents in Kilimanjaro Region","volume":"20","author":"Buchanan","year":"2015","journal-title":"Trop Med Int Health"},{"key":"2025121514561666000_8.7.e021817.36","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aan4669"},{"key":"2025121514561666000_8.7.e021817.37","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0509592103"},{"key":"2025121514561666000_8.7.e021817.38","first-page":"381","volume-title":"Annual Review of Food Science and Technology","volume":"4","author":"Claus","year":"2013"},{"key":"2025121514561666000_8.7.e021817.39","doi-asserted-by":"crossref","DOI":"10.1186\/1471-2105-12-271","article-title":"DNACLUST: accurate and efficient clustering of phylogenetic marker genes","volume":"12","author":"Ghodsi","year":"2011","journal-title":"BMC Bioinformatics"},{"key":"2025121514561666000_8.7.e021817.40","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.02658-12"},{"key":"2025121514561666000_8.7.e021817.41","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0158199","article-title":"Optimization of Quantitative PCR Methods for Enteropathogen Detection","volume":"11","author":"Liu","year":"2016","journal-title":"PLoS One"},{"key":"2025121514561666000_8.7.e021817.42","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6737(16)31529-X"},{"key":"2025121514561666000_8.7.e021817.43","unstructured":"Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing. 27 ed. Wayne, Pennsylvania: Clinical and Laboratory Standards Institute, 2017."},{"key":"2025121514561666000_8.7.e021817.44","first-page":"971","article-title":"Polymorphisms of two fucosyltransferase genes (Lewis and Secretor genes) involving type I Lewis antigens are associated with the presence of anti-Helicobacter pylori IgG antibody","volume":"10","author":"Ikehara","year":"2001","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"2025121514561666000_8.7.e021817.45","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddq248"},{"key":"2025121514561666000_8.7.e021817.46","doi-asserted-by":"publisher","DOI":"10.1086\/432546"},{"key":"2025121514561666000_8.7.e021817.47","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1600177"},{"key":"2025121514561666000_8.7.e021817.48","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.115.120055"},{"key":"2025121514561666000_8.7.e021817.49","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)60437-7"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2018-021817","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T22:56:23Z","timestamp":1765839383000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2018-021817"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,7]]},"references-count":49,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2018,7,7]]},"published-print":{"date-parts":[[2018,7]]}},"alternative-id":["10.1136\/bmjopen-2018-021817"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2018-021817","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,7]]}}}