title: Hepatosplenomegaly is associated with low regulatory and Th2 responses to schistosome antigens in childhood schistosomiasis and malaria coinfection.
abstract: Hepatosplenomegaly among Kenyan schoolchildren has been shown to be exacerbated where there is transmission of both Schistosoma mansoni and Plasmodium falciparum. This highly prevalent and chronic morbidity often occurs in the absence of ultrasound-detectable periportal fibrosis and may be due to immunological inflammation. For a cohort of school-age children, whole-blood cultures were stimulated with S. mansoni soluble egg antigen (SEA) or soluble worm antigen (SWA). Responses to SWA were found to be predominantly Th2 cytokines; however, they were not significantly associated with either hepatosplenomegaly or infection with S. mansoni or P. falciparum. In comparison, SEA-specific Th2 cytokine responses were low, and the levels were negatively correlated with S. mansoni infection intensities and were lower among children who were coinfected with P. falciparum. Tumor necrosis factor alpha levels in response to stimulation with SEA were high, and a negative association between presentation with hepatomegaly and the levels of the regulatory cytokines interleukin-6 and transforming growth factor beta(1) suggests that a possible mechanism for childhood hepatomegaly in areas where both malaria and schistosomiasis are endemic is poor regulation of an inflammatory response to schistosome eggs.
authors.affiliation: Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QP, United Kingdom. sw320@cam.ac.uk
authors.forename: Shona
authors.initials: S
authors.lastname: Wilson
authors.forename: Frances M
authors.initials: FM
authors.lastname: Jones
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Mwatha
authors.forename: Gachuhi
authors.initials: G
authors.lastname: Kimani
authors.forename: Mark
authors.initials: M
authors.lastname: Booth
authors.forename: H Curtis
authors.initials: HC
authors.lastname: Kariuki
authors.forename: Birgitte J
authors.initials: BJ
authors.lastname: Vennervald
authors.forename: John H
authors.initials: JH
authors.lastname: Ouma
authors.forename: Eric
authors.initials: E
authors.lastname: Muchiri
authors.forename: David W
authors.initials: DW
authors.lastname: Dunne
mesh_terms: D000293:Adolescent; D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000096:biosynthesis; D016054:DNA, Protozoan / Q000097:blood; D006529:Hepatomegaly / Q000276:immunology / Q000469:parasitology*; D006801:Humans; D007630:Kenya; D007963:Leukocytes, Mononuclear / Q000276:immunology; D016778:Malaria, Falciparum / Q000150:complications* / Q000276:immunology / Q000473:pathology*; D018512:Parasitemia; D010963:Plasmodium falciparum / Q000276:immunology / Q000302:isolation & purification; D016133:Polymerase Chain Reaction; D012550:Schistosoma mansoni / Q000276:immunology / Q000302:isolation & purification; D012552:Schistosomiasis / Q000150:complications* / Q000276:immunology / Q000473:pathology*; D013163:Splenomegaly / Q000276:immunology / Q000469:parasitology*; D018418:Th2 Cells / Q000276:immunology
chemical_list: D000953:Antigens, Protozoan; D016207:Cytokines; D016054:DNA, Protozoan