{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T06:57:02Z","timestamp":1778914622996,"version":"3.51.4"},"update-to":[{"DOI":"10.1371\/journal.pntd.0011455","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,11,29]],"date-time":"2023-11-29T00:00:00Z","timestamp":1701216000000}}],"reference-count":52,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T00:00:00Z","timestamp":1700006400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"H3Africa","award":["H3A-18-004"],"award-info":[{"award-number":["H3A-18-004"]}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:p>Over 290 million people are infected by schistosomes worldwide. Schistosomiasis control efforts focus on mass drug treatment with praziquantel (PZQ), a drug that kills the adult worm of all <jats:italic>Schistosoma<\/jats:italic> species. Nonetheless, re-infections have continued to be detected in endemic areas with individuals living in the same area presenting with varying infection intensities. Our objective was to characterize the transcriptome profiles in peripheral blood of children between 10\u201315 years with varying intensities of <jats:italic>Schistosoma mansoni<\/jats:italic> infection living along the Albert Nile in Uganda. RNA extracted from peripheral blood collected from 44 <jats:italic>S<\/jats:italic>. <jats:italic>mansoni<\/jats:italic> infected (34 high and 10 low by circulating anodic antigen [CAA] level) and 20 uninfected children was sequenced using Illumina NovaSeq S4 and the reads aligned to the GRCh38 human genome. Differential gene expression analysis was done using DESeq2. Principal component analysis revealed clustering of gene expression by gender when <jats:italic>S<\/jats:italic>. <jats:italic>mansoni<\/jats:italic> infected children were compared with uninfected children. In addition, we identified 14 DEGs between <jats:italic>S<\/jats:italic>. <jats:italic>mansoni<\/jats:italic> infected and uninfected individuals, 56 DEGs between children with high infection intensity and uninfected individuals, 33 DEGs between those with high infection intensity and low infection intensity and no DEGs between those with low infection and uninfected individuals. We also observed upregulation and downregulation of some DEGs that are associated with fibrosis and its regulation. These data suggest expression of fibrosis associated genes as well as genes that regulate fibrosis in <jats:italic>S<\/jats:italic>. <jats:italic>mansoni<\/jats:italic> infection. The relatively few significant DEGS observed in children with schistosomiasis suggests that chronic <jats:italic>S<\/jats:italic>. <jats:italic>mansoni<\/jats:italic> infection is a stealth infection that does not stimulate a strong immune response.<\/jats:p>","DOI":"10.1371\/journal.pntd.0011455","type":"journal-article","created":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T18:40:06Z","timestamp":1700073606000},"page":"e0011455","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["Transcriptome analysis of peripheral blood of Schistosoma mansoni infected children from the Albert Nile region in Uganda reveals genes implicated in fibrosis pathology"],"prefix":"10.1371","volume":"17","author":[{"given":"Joyce","family":"Namulondo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oscar Asanya","family":"Nyangiri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Magambo Phillip","family":"Kimuda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Nambala","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacent","family":"Nassuuna","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moses","family":"Egesa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Nerima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Savino","family":"Biryomumaisho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claire Mack","family":"Mugasa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Immaculate","family":"Nabukenya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Drago","family":"Kato","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alison","family":"Elliott","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harry","family":"Noyes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Tweyongyere","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enock","family":"Matovu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5419-2760","authenticated-orcid":true,"given":"Julius","family":"Mulindwa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"for the TrypanoGEN+ research group of the H3Africa consortium","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2023,11,15]]},"reference":[{"key":"pntd.0011455.ref001","doi-asserted-by":"crossref","first-page":"2253","DOI":"10.1016\/S0140-6736(13)61949-2","article-title":"Human schistosomiasis.","volume":"383","author":"DG Colley","year":"2014","journal-title":"Lancet"},{"key":"pntd.0011455.ref002","first-page":"629","article-title":"Schistosomiasis and soil-transmitted helminthiases: numbers of people treated in 2019 \u2013Schistosomiase et g\u00e9ohelminthiases: nombre de personnes trait\u00e9es en 2019.","volume":"95","author":"WHO","year":"2020","journal-title":"Weekly Epidemiological Record = Relev\u00e9 \u00e9pid\u00e9miologique hebdomadaire."},{"key":"pntd.0011455.ref003","doi-asserted-by":"crossref","first-page":"e2268","DOI":"10.1371\/journal.pntd.0002268","article-title":"A Very High Infection Intensity of Schistosoma mansoni in a Ugandan Lake Victoria Fishing Community Is Required for Association with Highly Prevalent Organ Related Morbidity.","volume":"7","author":"EM Tukahebwa","year":"2013","journal-title":"PLoS Negl Trop Dis."},{"key":"pntd.0011455.ref004","doi-asserted-by":"crossref","first-page":"e0010570","DOI":"10.1371\/journal.pntd.0010570","article-title":"High prevalence of Schistosoma mansoni infection and stunting among school age children in communities along the Albert-Nile, Northern Uganda: A cross sectional study.","volume":"16","author":"J Mulindwa","year":"2022","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0011455.ref005","doi-asserted-by":"crossref","first-page":"e0007617","DOI":"10.1371\/journal.pntd.0007617","article-title":"The prevalence of schistosomiasis in Uganda: A nationally representative population estimate to inform control programs and water and sanitation interventions.","volume":"13","author":"NG Exum","year":"2019","journal-title":"PLoS Negl Trop Dis. 2019\/08\/15"},{"key":"pntd.0011455.ref006","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1016\/j.actatropica.2018.06.009","article-title":"The epidemiology of schistosomiasis in Lango region Uganda 60 years after Schwetz 1951: Can schistosomiasis be eliminated through mass drug administration without other supportive control measures?","volume":"185","author":"M Adriko","year":"2018","journal-title":"Acta Trop"},{"key":"pntd.0011455.ref007","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1016\/j.dib.2018.08.200","article-title":"Data on the pre-MDA and post MDA interventions for Schistosoma mansoni and Schistosoma haematobium in a co-endemic focus in Uganda: 1951\u20132011.","volume":"20","author":"M Adriko","year":"2018","journal-title":"Data Brief."},{"key":"pntd.0011455.ref008","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/S0001-706X(00)00115-7","article-title":"Immunodiagnosis of schistosomiasis by determination of the circulating antigens CAA and CCA, in particular in individuals with recent or light infections","volume":"77","author":"L Van Lieshout","year":"2000","journal-title":"Acta Trop"},{"key":"pntd.0011455.ref009","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1046\/j.1365-3156.1997.d01-324.x","article-title":"Detection of the circulating antigens CAA and CCA in a group of Dutch travellers with acute schistosomiasis","volume":"2","author":"L Van Lieshout","year":"1997","journal-title":"Tropical Medicine and International Health"},{"key":"pntd.0011455.ref010","doi-asserted-by":"crossref","first-page":"50","DOI":"10.4269\/ajtmh.19-0819","article-title":"Circulating Anodic Antigen (CAA): A Highly Sensitive Diagnostic Biomarker to Detect Active Schistosoma Infections\u2014Improvement and Use during SCORE.","volume":"103","author":"PLAM Corstjens","year":"2020","journal-title":"Am J Trop Med Hyg"},{"key":"pntd.0011455.ref011","first-page":"4","article-title":"Co-ordinated gene expression in the liver and spleen during Schistosoma japonicum infection regulates cell migration","author":"ML Burke","year":"2010","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0011455.ref012","first-page":"4","article-title":"Temporal expression of chemokines dictates the hepatic inflammatory infiltrate in a murine model of schistosomiasis.","author":"ML Burke","year":"2010","journal-title":"PLoS Negl Trop Dis."},{"key":"pntd.0011455.ref013","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1189\/jlb.1212653","article-title":"Spatial and temporal transcriptomics of Schistosoma japonicum -induced hepatic granuloma formation reveals novel roles for neutrophils","volume":"94","author":"C Chuah","year":"2013","journal-title":"J Leukoc Biol"},{"key":"pntd.0011455.ref014","doi-asserted-by":"crossref","first-page":"e0130344","DOI":"10.1371\/journal.pone.0130344","article-title":"The differential expression of immune genes between water buffalo and yellow cattle determines species-specific susceptibility to Schistosoma japonicum infection.","volume":"10","author":"J Yang","year":"2015","journal-title":"PLoS One"},{"key":"pntd.0011455.ref015","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/IAI.00291-18","article-title":"Gene expression differences in host response to Schistosoma haematobium infection","volume":"87","author":"KM Dupnik","year":"2019","journal-title":"Infect Immun"},{"key":"pntd.0011455.ref016","doi-asserted-by":"crossref","first-page":"1841","DOI":"10.1017\/S0031182014000626","article-title":"Tools for diagnosis, monitoring and screening of Schistosoma infections utilizing lateral-flow based assays and upconverting phosphor labels","volume":"141","author":"De Dood CJ Corstjens PLAM","year":"2014","journal-title":"Parasitology"},{"key":"pntd.0011455.ref017","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/978-1-0716-0294-2_6","article-title":"High-Throughput Sequencing for Trypanosome Transcriptome Characterization","volume":"2116","author":"J Mulindwa","year":"2020","journal-title":"Methods Mol Biol"},{"key":"pntd.0011455.ref018","first-page":"1","article-title":"Comparison of three different kits for extraction of high-quality RNA from frozen blood","volume":"3","author":"JH Kim","year":"2014","journal-title":"Springerplus"},{"key":"pntd.0011455.ref019","doi-asserted-by":"crossref","first-page":"D884","DOI":"10.1093\/nar\/gkaa942","article-title":"Ensembl 2021","volume":"49","author":"KL Howe","year":"2021","journal-title":"Nucleic Acids Res"},{"key":"pntd.0011455.ref020","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1038\/s41587-019-0201-4","article-title":"Graph-based genome alignment and genotyping with HISAT2 and HISAT-genotype","volume":"37","author":"D Kim","year":"2019","journal-title":"Nat Biotechnol"},{"key":"pntd.0011455.ref021","first-page":"1","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"MI Love","year":"2014","journal-title":"Genome Biol"},{"key":"pntd.0011455.ref022","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12859-019-2879-1","article-title":"PcaExplorer: An R\/Bioconductor package for interacting with RNA-seq principal components","volume":"20","author":"F Marini","year":"2019","journal-title":"BMC Bioinformatics"},{"key":"pntd.0011455.ref023","first-page":"1","article-title":"Accurate estimation of cell composition in bulk expression through robust integration of single-cell information","volume":"11","author":"B Jew","year":"2020","journal-title":"Nature Communications 2020 11:1."},{"key":"pntd.0011455.ref024","first-page":"8","article-title":"Single-cell transcriptomic landscape of human blood cells","author":"X Xie","year":"2021","journal-title":"Natl Sci Rev"},{"key":"pntd.0011455.ref025","first-page":"4669","article-title":"Acute and Chronic Changes in Gene Expression After CMV DNAemia in Kidney Transplant Recipients.","volume":"12","author":"R Ahn","year":"2021","journal-title":"Front Immunol"},{"key":"pntd.0011455.ref026","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1093\/cid\/ciw767","article-title":"RNA-Seq Analysis of Gene Expression, Viral Pathogen, and B-Cell\/T-Cell Receptor Signatures in Complex Chronic Disease","volume":"64","author":"J Bouquet","year":"2017","journal-title":"Clinical Infectious Diseases"},{"key":"pntd.0011455.ref027","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0204912","article-title":"Whole-exome sequencing capture kit biases yield false negative mutation calls in TCGA cohorts","author":"VG Wang","year":"2018"},{"key":"pntd.0011455.ref028","first-page":"30","article-title":"Whole-exome sequencing of rectal neuroendocrine tumors","author":"Y Li","year":"2023","journal-title":"Endocr Relat Cancer"},{"key":"pntd.0011455.ref029","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1089\/wound.2015.0658","article-title":"Targeting Microtubules for Wound Repair.","volume":"5","author":"RA Charafeddine","year":"2016","journal-title":"Adv Wound Care (New Rochelle)."},{"key":"pntd.0011455.ref030","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1111\/tra.12629","article-title":"CLIP-170 spatially modulates receptor tyrosine kinase recycling to coordinate cell migration","volume":"20","author":"K Zaoui","year":"2019","journal-title":"Traffic"},{"key":"pntd.0011455.ref031","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1083\/jcb.201411045","article-title":"IQGAP1 promotes CXCR4 chemokine receptor function and trafficking via EEA-1+ endosomes","volume":"210","author":"AO Bamidele","year":"2015","journal-title":"J Cell Biol"},{"key":"pntd.0011455.ref032","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.molimm.2019.04.014","article-title":"The role of microtubules in the immune system and as potential targets for gut-based immunotherapy","volume":"111","author":"T Ilan-Ber","year":"2019","journal-title":"Mol Immunol"},{"key":"pntd.0011455.ref033","first-page":"5","article-title":"Differential expression of chemokine and matrix re-modelling genes is associated with contrasting schistosome-induced hepatopathology in murine models","author":"CR Perry","year":"2011","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0011455.ref034","first-page":"7","article-title":"Identification of key genes, pathways and potential therapeutic agents for liver fibrosis using an integrated bioinformatics analysis","author":"Z Zhan","year":"2019","journal-title":"PeerJ"},{"key":"pntd.0011455.ref035","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/nrneph.2016.48","article-title":"TGF-\u03b2: the master regulator of fibrosis.","volume":"12","author":"XM Meng","year":"2016","journal-title":"Nat Rev Nephrol"},{"key":"pntd.0011455.ref036","first-page":"9","article-title":"Loss of microRNA-128 promotes cardiomyocyte proliferation and heart regeneration","author":"W Huang","year":"2018","journal-title":"Nat Commun"},{"key":"pntd.0011455.ref037","first-page":"2019","article-title":"P27 Promotes TGF- \u03b2-Mediated Pulmonary Fibrosis via Interacting with MTORC2.","author":"YH Dai","year":"2019","journal-title":"Can Respir J."},{"key":"pntd.0011455.ref038","first-page":"2020","article-title":"C1q\/TNF-Related Protein 9 Inhibits Coxsackievirus B3-Induced Injury in Cardiomyocytes through NF- \u03ba B and TGF- \u03b2 1\/Smad2\/3 by Modulating THBS1.","author":"K Liu","year":"2020","journal-title":"Mediators Inflamm."},{"key":"pntd.0011455.ref039","doi-asserted-by":"crossref","first-page":"13461","DOI":"10.1096\/fj.201901291RRRRR","article-title":"8-Oxoguanine DNA glycosylase modulates the cell transformation process in pulmonary fibrosis by inhibiting Smad2\/3 and interacting with Smad7","volume":"34","author":"Y Wang","year":"2020","journal-title":"FASEB J"},{"key":"pntd.0011455.ref040","first-page":"12","article-title":"Analysis of the whole transcriptome from gingivo-buccal squamous cell carcinoma reveals deregulated immune landscape and suggests targets for immunotherapy","author":"R Singh","year":"2017","journal-title":"PLoS One"},{"key":"pntd.0011455.ref041","first-page":"5","article-title":"Whole-blood RNA transcript-based models can predict clinical response in two large independent clinical studies of patients with advanced melanoma treated with the checkpoint inhibitor, tremelimumab","author":"P Friedlander","year":"2017","journal-title":"J Immunother Cancer"},{"key":"pntd.0011455.ref042","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1097\/DAD.0b013e31825ba13f","article-title":"A snapshot of gene expression signatures generated using microarray datasets associated with excessive scarring","volume":"35","author":"C Huang","year":"2013","journal-title":"Am J Dermatopathol"},{"key":"pntd.0011455.ref043","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.joen.2011.09.011","article-title":"Expression analysis of wound healing genes in human periapical granulomas of progressive and stable nature","volume":"38","author":"GP Garlet","year":"2012","journal-title":"J Endod"},{"key":"pntd.0011455.ref044","first-page":"22","article-title":"LncRNA MALAT1 Modulates TGF-\u03b21-Induced EMT in Keratinocyte.","author":"L Zhang","year":"2021","journal-title":"Int J Mol Sci."},{"key":"pntd.0011455.ref045","first-page":"5","article-title":"Fortilin interacts with TGF-\u03b21 and prevents TGF-\u03b2 receptor activation","author":"D Pinkaew","year":"2022","journal-title":"Commun Biol"},{"key":"pntd.0011455.ref046","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1161\/CIRCRESAHA.110.226613","article-title":"The critical role of neutral cholesterol ester hydrolase 1 in cholesterol removal from human macrophages","volume":"107","author":"M Igarashi","year":"2010","journal-title":"Circ Res"},{"key":"pntd.0011455.ref047","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1080\/17476348.2018.1506331","article-title":"The effect of obesity on lung function","volume":"12","author":"AE Dixon","year":"2018","journal-title":"Expert Rev Respir Med"},{"key":"pntd.0011455.ref048","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12931-021-01920-8","article-title":"MUC5B regulates goblet cell differentiation and reduces inflammation in a murine COPD model","volume":"23","author":"X Huang","year":"2022","journal-title":"Respir Res"},{"key":"pntd.0011455.ref049","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.1182\/blood-2017-06-780882","article-title":"Inflammation: a key regulator of hematopoietic stem cell fate in health and disease","volume":"130","author":"EM Pietras","year":"2017","journal-title":"Blood"},{"key":"pntd.0011455.ref050","first-page":"3342","article-title":"Mobilized Multipotent Hematopoietic Progenitors Stabilize and Expand Regulatory T Cells to Protect Against Autoimmune Encephalomyelitis.","volume":"11","author":"D Korniotis S","year":"2020","journal-title":"Front Immunol."},{"key":"pntd.0011455.ref051","doi-asserted-by":"crossref","first-page":"1821","DOI":"10.3389\/fimmu.2020.01821","article-title":"Clinical Use of Schistosoma mansoni Antigens as Novel Immunotherapies for Autoimmune Disorders.","volume":"11","author":"L Cleenewerk","year":"2020","journal-title":"Front Immunol."},{"key":"pntd.0011455.ref052","doi-asserted-by":"crossref","first-page":"e105017","DOI":"10.1371\/journal.pone.0105017","article-title":"The Immune System in Children with Malnutrition\u2014A Systematic Review.","volume":"9","author":"MJH Rytter","year":"2014","journal-title":"PLoS One."}],"updated-by":[{"DOI":"10.1371\/journal.pntd.0011455","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,11,29]],"date-time":"2023-11-29T00:00:00Z","timestamp":1701216000000}}],"container-title":["PLOS Neglected Tropical Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0011455","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,29]],"date-time":"2023-11-29T18:45:20Z","timestamp":1701283520000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0011455"}},"subtitle":[],"editor":[{"given":"Jennifer A.","family":"Downs","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2023,11,15]]},"references-count":52,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2023,11,15]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pntd.0011455","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.pntd.0011455","asserted-by":"object"}]},"ISSN":["1935-2735"],"issn-type":[{"value":"1935-2735","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,15]]}}}