{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T18:12:09Z","timestamp":1779300729870,"version":"3.51.4"},"update-to":[{"DOI":"10.1371\/journal.pntd.0013734","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000}}],"reference-count":38,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:00:00Z","timestamp":1778803200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015691","name":"Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI127845"],"award-info":[{"award-number":["R01AI127845"]}],"id":[{"id":"10.13039\/100015691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000061","name":"Fogarty International Center","doi-asserted-by":"publisher","award":["D43 TW010923"],"award-info":[{"award-number":["D43 TW010923"]}],"id":[{"id":"10.13039\/100000061","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015691","name":"Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI151214"],"award-info":[{"award-number":["R01AI151214"]}],"id":[{"id":"10.13039\/100015691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015691","name":"Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["K24AI141744"],"award-info":[{"award-number":["K24AI141744"]}],"id":[{"id":"10.13039\/100015691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Giardia lamblia<\/jats:italic>\n                      (\n                      <jats:italic>Giardia<\/jats:italic>\n                      ) is one of the most common intestinal parasitic infections globally, with an estimated 280 million symptomatic infections annually. In children from low- and middle-income countries (LMICs),\n                      <jats:italic>Giardia<\/jats:italic>\n                      is highly prevalent and has been associated with loss of intestinal barrier function, nutrient-metabolic dysregulation, and linear growth impairment, but specific mechanisms linking\n                      <jats:italic>Giardia<\/jats:italic>\n                      to these outcomes remain poorly understood.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>\n                      We used data and samples from a subset of 76 children in a longitudinal birth cohort in Nicaragua to evaluate the natural history and geospatial distribution of\n                      <jats:italic>Giardia<\/jats:italic>\n                      infections, child growth outcomes (weight-for-age [WAZ] and length-for-age [LAZ] z scores), and relationships with established biomarkers of inflammation, intestinal damage, and growth-signaling. During the first 36 months of life, we tested 2,305 stools (1,903 surveillance stools and 402 diarrheal stools) for\n                      <jats:italic>Giardia<\/jats:italic>\n                      by qPCR. The incidence of\n                      <jats:italic>Giardia<\/jats:italic>\n                      -positive stools was 59.6 per 100 child-years. Any detection of\n                      <jats:italic>Giardia<\/jats:italic>\n                      was associated with a reduction in LAZ at 36 months of life (\u03b2:-0.16,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.042). This effect increased when considering persistent or recurrent\n                      <jats:italic>Giardia<\/jats:italic>\n                      detections (\u03b2:-0.26,\n                      <jats:italic>P<\/jats:italic>\n                      =&lt;0.001) as well as living in a high-density\n                      <jats:italic>Giardia<\/jats:italic>\n                      detection area (\u03b2:-0.44, P=&lt;0.001). Among intestinal markers,\n                      <jats:italic>Giardia<\/jats:italic>\n                      was associated with lower median fecal neopterin (a marker of chronic intestinal T cell activation) at 24 and 36 months of age. Among serum systemic biomarkers measured at 24 months,\n                      <jats:italic>Giardia<\/jats:italic>\n                      detections were associated with indicators of intestinal epithelial cell damage (higher median Intestinal Fatty Acid Binding Protein (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.002) and Anti-FliC IgA (P\u2009=\u20090.033), and reduced growth-signaling hormone (lower median Insulin-like Growth Factor (IGF-1) (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.005).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Giardia<\/jats:italic>\n                      detection was negatively associated with linear growth in an exposure-dependent manner. Simultaneously,\n                      <jats:italic>Giardia<\/jats:italic>\n                      was associated with diminished serum growth-signaling hormones. Patterns of serum and fecal intestinal biomarkers suggest that\n                      <jats:italic>Giardia-<\/jats:italic>\n                      mediated epithelial disruption is dissociated from markers of intestinal inflammation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pntd.0013734","type":"journal-article","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T17:44:07Z","timestamp":1778867047000},"page":"e0013734","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Natural history and impact of Giardia lamblia on child growth attainment and associated pathway-specific biomarkers in a Nicaraguan birth cohort"],"prefix":"10.1371","volume":"20","author":[{"given":"Lester","family":"Guti\u00e9rrez","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadja A.","family":"Vielot","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaoska","family":"Reyes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberto","family":"Herrera","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Toval-Ruiz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Javier","family":"Mora","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael B.","family":"Arndt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca","family":"Barney","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert K.M.","family":"Choy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Filem\u00f3n","family":"Bucardo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel","family":"Vilchez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7808-2507","authenticated-orcid":true,"given":"Sylvia","family":"Becker-Dreps","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luther A.","family":"Bartelt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,5,15]]},"reference":[{"issue":"1","key":"pntd.0013734.ref001","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1128\/CMR.00067-12","article-title":"Transmission and epidemiology of zoonotic protozoal diseases of companion animals","volume":"26","author":"KJ Esch","year":"2013","journal-title":"Clin Microbiol Rev"},{"key":"pntd.0013734.ref002","first-page":"15","article-title":"Giardiasis Surveillance \u2014 United States, 2011\u20132012","volume":"64","author":"J Painter","year":"2015","journal-title":"MMWR Surveill Summ"},{"key":"pntd.0013734.ref003","article-title":"Pathogenic mechanisms of Cryptosporidium and Giardia","author":"G Certad","year":"2017","journal-title":"Trends in Parasitology"},{"issue":"2","key":"pntd.0013734.ref004","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":"ET Rogawski","year":"2017","journal-title":"J Pediatric Infect Dis Soc"},{"issue":"12","key":"pntd.0013734.ref005","doi-asserted-by":"crossref","DOI":"10.1016\/S2214-109X(18)30351-6","article-title":"Use of quantitative molecular diagnostic methods to investigate the effect of enteropathogen infections on linear growth in children in low-resource settings: longitudinal analysis of results from the MAL-ED cohort study","volume":"6","author":"ET Rogawski","year":"2018","journal-title":"Lancet Glob Health"},{"issue":"8","key":"pntd.0013734.ref006","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0221095","article-title":"Pathobiome driven gut inflammation in Pakistani children with Environmental Enteric Dysfunction","volume":"14","author":"NT Iqbal","year":"2019","journal-title":"PLoS One"},{"issue":"11","key":"pntd.0013734.ref007","first-page":"371","article-title":"Intestinal Parasitic Infection and Nutritional Status in Children under Five Years Old: A Systematic Review","volume":"7","author":"N Fauziah","year":"2022","journal-title":"Trop Med Infect Dis"},{"issue":"1","key":"pntd.0013734.ref008","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1093\/tropej\/49.1.17","article-title":"Predictors and nutritional consequences of intestinal parasitic infections in rural Ecuadorian children","volume":"49","author":"M-E Sackey","year":"2003","journal-title":"J Trop Pediatr"},{"key":"pntd.0013734.ref009","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1590\/S0036-46652007000300003","article-title":"Giardia lamblia and other intestinal parasitic infections and their relationships with nutritional status in children in Brazilian Amazon","volume":"49","author":"FA Carvalho-Costa","year":"2007","journal-title":"Rev Inst Med Trop Sao Paulo"},{"issue":"10","key":"pntd.0013734.ref010","article-title":"Symptomatic and asymptomatic enteric protozoan parasitic infection and their association with subsequent growth parameters in under five children in South Asia and sub-Saharan Africa","volume":"17","author":"R Das","year":"2023","journal-title":"PLoS Negl Trop Dis"},{"issue":"1","key":"pntd.0013734.ref011","doi-asserted-by":"crossref","first-page":"2840","DOI":"10.1038\/s41467-023-38363-2","article-title":"Giardia hinders growth by disrupting nutrient metabolism independent of inflammatory enteropathy","volume":"14","author":"N Giallourou","year":"2023","journal-title":"Nat Commun"},{"issue":"1","key":"pntd.0013734.ref012","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1007\/s40475-024-00314-2","article-title":"Current Understanding of Giardia lamblia and Pathogenesis of Stunting and Cognitive Deficits in Children from Low- and Middle-Income Countries","volume":"11","author":"L Guti\u00e9rrez","year":"2024","journal-title":"Curr Trop Med Rep"},{"issue":"3","key":"pntd.0013734.ref013","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1203\/01.PDR.0000076666.16021.5E","article-title":"Chronic T cell-mediated enteropathy in rural west African children: relationship with nutritional status and small bowel function","volume":"54","author":"DI Campbell","year":"2003","journal-title":"Pediatr Res"},{"key":"pntd.0013734.ref014","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.ebiom.2017.02.024","article-title":"Causal Pathways from Enteropathogens to Environmental Enteropathy: Findings from the MAL-ED Birth Cohort Study","volume":"18","author":"MAL-ED Network Investigators","year":"2017","journal-title":"EBioMedicine"},{"issue":"3","key":"pntd.0013734.ref015","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1097\/INF.0000000000003015","article-title":"Risk Factors and Clinical Profile of Sapovirus-associated Acute Gastroenteritis in Early Childhood: A Nicaraguan Birth Cohort Study","volume":"40","author":"NA Vielot","year":"2021","journal-title":"Pediatr Infect Dis J"},{"issue":"11","key":"pntd.0013734.ref016","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0012230","article-title":"Giardia lamblia risk factors and burden in children with acute gastroenteritis in a Nicaraguan birth cohort","volume":"18","author":"L Guti\u00e9rrez","year":"2024","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0013734.ref017","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1099\/jmm.0.46678-0","article-title":"Real-time PCR detection and speciation of Cryptosporidium infection using Scorpion probes","volume":"55","author":"SE Stroup","year":"2006","journal-title":"J Med Microbiol"},{"issue":"5","key":"pntd.0013734.ref018","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/S0890-8508(03)00057-4","article-title":"Real-time PCR for the detection of Giardia lamblia","volume":"17","author":"JJ Verweij","year":"2003","journal-title":"Mol Cell Probes"},{"issue":"9","key":"pntd.0013734.ref019","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0008711","article-title":"Validation of the Micronutrient and Environmental Enteric Dysfunction Assessment Tool and evaluation of biomarker risk factors for growth faltering and vaccine failure in young Malian children","volume":"14","author":"MB Arndt","year":"2020","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0013734.ref020","doi-asserted-by":"crossref","first-page":"64","DOI":"10.2105\/AJPH.90.1.64","article-title":"The effect of poverty, social inequity, and maternal education on infant mortality in Nicaragua, 1988-1993","volume":"90","author":"R Pe\u00f1a","year":"2000","journal-title":"Am J Public Health"},{"key":"pntd.0013734.ref021","volume-title":"WHO Child Growth Standards: Length\/height-for-age, weight-for-age, weight-for-length, weight-forheight and body mass index-for-age: methods and development","author":"World Health Organization","year":"2006"},{"issue":"5","key":"pntd.0013734.ref022","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1213\/ANE.0000000000002864","article-title":"Correlation Coefficients: Appropriate Use and Interpretation","volume":"126","author":"P Schober","year":"2018","journal-title":"Anesth Analg"},{"issue":"11","key":"pntd.0013734.ref023","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1097\/INF.0000000000000427","article-title":"Etiology of childhood diarrhea after rotavirus vaccine introduction: a prospective, population-based study in Nicaragua","volume":"33","author":"S Becker-Dreps","year":"2014","journal-title":"Pediatr Infect Dis J"},{"key":"pntd.0013734.ref024","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1007\/s00436-023-07798-3","article-title":"Change in the incidence of intestinal diseases caused by parasitic protozoa in the Mexican population during the period (2015-2019) and its association with environmental and socioeconomic risk factors","volume":"122","author":"F Guti\u00e9rrez-Guti\u00e9rrez","year":"2023","journal-title":"Parasitol Res"},{"issue":"3","key":"pntd.0013734.ref025","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0005445","article-title":"Geospatial distribution of intestinal parasitic infections in Rio de Janeiro (Brazil) and its association with social determinants","volume":"11","author":"CP Faria","year":"2017","journal-title":"PLoS Negl Trop Dis"},{"issue":"5","key":"pntd.0013734.ref026","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.idnow.2022.04.005","article-title":"Giardia lamblia infection and associated risk factors among patients attending Kochore Health Center, Ethiopia","volume":"52","author":"ST Hajare","year":"2022","journal-title":"Infect Dis Now"},{"issue":"12","key":"pntd.0013734.ref027","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgph.0002631","article-title":"Improved household flooring is associated with lower odds of enteric and parasitic infections in low- and middle-income countries: A systematic review and meta-analysis","volume":"3","author":"H Legge","year":"2023","journal-title":"PLOS Glob Public Health"},{"issue":"6","key":"pntd.0013734.ref028","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2024-090464","article-title":"Evaluating impacts of improved flooring on enteric and parasitic infections in rural households in Kenya: study protocol for a cluster-randomised controlled trial","volume":"15","author":"KE Halliday","year":"2025","journal-title":"BMJ Open"},{"issue":"1","key":"pntd.0013734.ref029","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1080\/21505594.2018.1451284","article-title":"Secreted Giardia intestinalis cysteine proteases disrupt intestinal epithelial cell junctional complexes and degrade chemokines","volume":"9","author":"J Liu","year":"2018","journal-title":"Virulence"},{"key":"pntd.0013734.ref030","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3390\/pathogens9010007","article-title":"Giardiasis Alters Intestinal Fatty Acid Binding Protein (I-FABP) and Plasma Cytokines Levels in Children in Brazil","volume":"9","author":"T Cascais-Figueiredo","year":"2019","journal-title":"Pathogens"},{"key":"pntd.0013734.ref031","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.nut.2016.06.013","article-title":"Systemic inflammation, growth factors, and linear growth in the setting of infection and malnutrition","volume":"33","author":"MD DeBoer","year":"2017","journal-title":"Nutrition"},{"issue":"1","key":"pntd.0013734.ref032","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1677\/jme.0.0060033","article-title":"Nutrition and somatomedin. XXII: Molecular regulation of insulin-like growth factor-I during fasting and refeeding in rats","volume":"6","author":"S Goldstein","year":"1991","journal-title":"J Mol Endocrinol"},{"issue":"12","key":"pntd.0013734.ref033","doi-asserted-by":"crossref","first-page":"2973","DOI":"10.3390\/nu11122973","article-title":"Giardia intestinalis and Fructose Malabsorption: A Frequent Association","volume":"11","author":"M Trelis","year":"2019","journal-title":"Nutrients"},{"issue":"1","key":"pntd.0013734.ref034","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1111\/j.1445-5994.1986.tb01127.x","article-title":"Giardia infection causes vitamin B12 deficiency","volume":"16","author":"FT Cordingley","year":"1986","journal-title":"Aust N Z J Med"},{"issue":"9","key":"pntd.0013734.ref035","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0136102","article-title":"Giardia duodenalis Surface Cysteine Proteases Induce Cleavage of the Intestinal Epithelial Cytoskeletal Protein Villin via Myosin Light Chain Kinase","volume":"10","author":"A Bhargava","year":"2015","journal-title":"PLoS One"},{"issue":"2","key":"pntd.0013734.ref036","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/BF00935423","article-title":"Growth, activities of enzymes in the small intestine, and ultrastructure of microvillous border in gerbils infected with Giardia duodenalis","volume":"77","author":"A Buret","year":"1991","journal-title":"Parasitol Res"},{"issue":"3","key":"pntd.0013734.ref037","doi-asserted-by":"crossref","first-page":"1570","DOI":"10.1210\/endo.134.3.7509741","article-title":"Differential regulation of insulin-like growth factor I (IGF-I) and IGF binding protein-1 messenger ribonucleic acids by amino acid availability and growth hormone in rat hepatocyte primary culture","volume":"134","author":"JP Thissen","year":"1994","journal-title":"Endocrinology"},{"issue":"4","key":"pntd.0013734.ref038","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1016\/j.bbrc.2019.05.044","article-title":"Arginine induces IGF-1 secretion from the endoplasmic reticulum","volume":"514","author":"Y Tsugawa","year":"2019","journal-title":"Biochem Biophys Res Commun"}],"updated-by":[{"DOI":"10.1371\/journal.pntd.0013734","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000}}],"container-title":["PLOS Neglected Tropical Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0013734","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T17:54:55Z","timestamp":1779299695000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0013734"}},"subtitle":[],"editor":[{"given":"Lars","family":"Eckmann","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2026,5,15]]},"references-count":38,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5,15]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pntd.0013734","relation":{},"ISSN":["1935-2735"],"issn-type":[{"value":"1935-2735","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,15]]}}}