Browsing by Author "Alison, Elliott"

Now showing 1 - 4 of 4
  • Thumbnail Image
    Item
    Candidate gene family-based and case-control studies of susceptibility to high Schistosoma mansoni worm burden in African children
    (AAS open research, 2021) Nyangiri, Oscar A.; Sokouri, A. Edwige; Koffi, Mathurin; Mewamba, Estelle; Simo, Gustave; Namulondo, Joyce; Mulindwa, Julius; Nassuuna, Jacent; Alison, Elliott; Karume, Kévin; Mumba, Dieudonne; M. Casacuberta-Partal; Dam, G. J. van; Bruno, Bucheton; Harry, Noyes; Matovu, Enock
    Background: Approximately 25% of the risk of Schistosoma mansoni is associated with host genetic variation. We will test 24 candidate genes, mainly in the T h2 and T h17 pathways, for association with S. mansoni infection intensity in four African countries, using family based and case-control approaches. Methods: Children aged 5-15 years will be recruited in S. mansoni endemic areas of Ivory Coast, Cameroon, Uganda and the Democratic Republic of Congo (DRC). We will use family based (study 1) and case-control (study 2) designs. Study 1 will take place in Ivory Coast, Cameroon, Uganda and the DRC. We aim to recruit 100 high worm burden families from each country except Uganda, where a previous study recruited at least 40 families. For phenotyping, cases will be defined as the 20% of children in each community with heaviest worm burdens as measured by the circulating cathodic antigen (CCA) assay. Study 2 will take place in Uganda. We will recruit 500 children in a highly endemic community. For phenotyping, cases will be defined as the 20% of children with heaviest worm burdens as measured by the CAA assay, while controls will be the 20% of infected children with the lightest worm burdens. Deoxyribonucleic acid (DNA) will be genotyped on the Illumina H3Africa SNP (single nucleotide polymorphisms) chip and genotypes will be converted to sets of haplotypes that span the gene region for analysis. We have selected 24 genes for genotyping that are mainly in the Th2 and Th17 pathways and that have variants that have been demonstrated to be or could be associated with Schistosoma infection intensity. Analysis: In the family-based design, we will identify SNP haplotypes disproportionately transmitted to children with high worm burden. Case-control analysis will detect overrepresentation of haplotypes in extreme phenotypes with correction for relatedness by using whole genome principal components.
  • Thumbnail Image
    Item
    Schistosoma mansoni coinfection is associated with high Plasmodium falciparum infection intensity among 10 -15 year old children living along the Albert Nile in Uganda
    (Research Sqaure, 2024) Namulondo, Joyce; Nyangiri, Oscar Asanya; Kimuda, Magambo Phillip; Nambala, Peter; Nassuuna, Jacent; Kabagenyi, Joyce; Egesa, Moses; Nerima, Barbara; Biryomumaisho, Savino; Mugasa, Claire Mack; Alison, Elliott; Harry, Noyes; Tweyongyere, Robert; Matovu, Enock; Mulindwa, Julius
    Background: Malaria and schistosomiasis are important parasitic diseases. Coinfections of these have been reported in areas endemic to both parasites. The aim of this study was to determine the association between Schistosoma mansoni (S. mansoni) and Plasmodium falciparum (P. falciparum) infection intensities among school age children living along the Albert Nile. Methods: A cross sectional study of 210 children aged 10–15 years, was conducted in selected sites along the Albert Nile in Pakwach District in northwest Uganda. The Circulating Anodic Antigen (CAA) test and quantitative PCR (qPCR) were used to test for S. mansoni infection intensity and quantitative PCR used to test for P. falciparum infection intensity. Results: Of the 210 study particpants, 76.2% (160/210) were malaria positive whereas 91% (191/210) were S. mansoni positive. There were only 1% (3/210) infections of each of Necator americanus and Strongyloides stercolaris. Of the P. falciparum positive children 57.5% (92/160) were male; on the other hand 53.4% (102/191) of the S. mansoni positive children were male. Overall, 150 of the 210 children tested (71%) had co-infection with both P. falciparum and S. mansoni. There was a significant association (p-value = 7.306e-10, r2  = 0.17) between P. falciparum qPCR Ct-value and S. mansoni qPCR Ct-value. There was a significant association (p-value = 7.306e-10, r2  = 0.17) between P. falciparum intensity (qPCR Ct-value) and S. mansoni intensity (qPCR Ct-value) among the children test. Conclusions: By molecular detection, this study observed a high prevalence of P. falciparum among the school age children (10–15 years) living in the S. mansoni endemic hotspots along the Albert-Nile region of Pakwach district, northwestern Uganda.
  • Thumbnail Image
    Item
    Transcriptome analysis of peripheral blood of Schistosoma mansoni infected children from the Albert Nile region in Uganda reveals genes implicated in fibrosis pathology
    (PLOS NEGLECTED TROPICAL DISEASES, 2023) Namulondo, Joyce; Nyangiri, Oscar Asanya; Kimuda, Magambo Phillip; Nambala, Peter; Nassuuna, Jacent; Egesa, Moses; Nerima, Barbara; Biryomumaisho, Savino; Mugasa, Claire Mack; Nabukenya, Immaculate; Kato, Drago; Alison, Elliott; Harry, Noye; Tweyongyere, Robert; Matovu, Enock; Mulindwa, Julius
    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 Schistosoma 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 10–15 years with varying intensities of Schistosoma mansoni infection living along the Albert Nile in Uganda. RNA extracted from peripheral blood collected from 44 S. mansoni 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 S. mansoni infected children were compared with uninfected children. In addition, we identified 14 DEGs between S. mansoni 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 S. mansoni infection. The relatively few significant DEGS observed in children with schistosomiasis suggests that chronic S. mansoni infection is a stealth infection that does not stimulate a strong immune response.
  • Thumbnail Image
    Item
    Variants of IL6, IL10, FCN2, RNASE3, IL12B and IL17B loci are associated with Schistosoma mansoni worm burden in the Albert Nile region of Uganda
    (PLOS NEGLECTED TROPICAL DISEASES, 2023) Nyangiri, Oscar Asanya; Mulindwa, Julius; Namulondo, Joyce; Kitibwa, Anna; Nassuuna, Jacent; Alison, Elliott; Kimuda, Magambo Phillip; Boobo, Alex; Nerima, Barbara; Adriko, Moses; Nathan, J. Dunton; Gaganjit, Kaur Madhan; Mark, Kristiansen; Miriam, Casacuberta-Partal; Harry, Noyes; Matovu, Enock
    Background Individuals genetically susceptible to high schistosomiasis worm burden may contribute disproportionately to transmission and could be prioritized for control. Identifying genes involved may guide development of therapy. Methodology/Principal findings A cohort of 606 children aged 10–15 years were recruited in the Albert Nile region of Uganda and assessed for Schistosoma mansoni worm burden using the Up-Converting Particle Lateral Flow (UCP-LF) test detecting circulating anodic antigen (CAA), point-of-care Circulating Cathodic Antigen (POC-CCA) and Kato-Katz tests. Whole genome genotyping was conducted on 326 children comprising the top and bottom 25% of worm burden. Linear models were fitted to identify variants associated with worm burden in preselected candidate genes. Expression quantitative trait locus (eQTL) analysis was conducted for candidate genes with UCP-LF worm burden included as a covariate. Single Nucleotide Polymorphism loci associated with UCP-LF CAA included IL6 rs2066992 (OR = 0.43, p = 0.0006) and rs7793163 (OR = 2.0, p = 0.0007); IL21 SNP kgp513476 (OR 1.79, p = 0.0025) and IL17B SNP kgp708159 (OR = 0.35, p = 0.0028). A haplotype in the IL10 locus was associated with lower worm burden (OR = 0.53, p = 0.015) and overlapped SNPs rs1800896, rs1800871 and rs1800872. Significant haplotypes (p<0.05, overlapping significant SNP) associated with worm burden were observed in IL6 and the Th17 pathway IL12B and IL17B genes. There were significant eQTL in the IL6, IL5, IL21, IL25 and IFNG regions. Conclusions Variants associated with S. mansoni worm burden were in IL6, FCN2, RNASE3, IL10, IL12B and IL17B gene loci. However only eQTL associations remained significant after Bonferroni correction. In summary, immune balance, pathogen recognition and Th17 pathways may play a role in modulating Schistosoma worm burden. Individuals carrying risk variants may be targeted first in allocation of control efforts to reduce the burden of schistosomiasis in the community.