Browsing by Author "Nerima, Barbara"

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    Differences in gene expression profiles in early and late stage rhodesiense HAT individuals in Malawi
    (PLoS neglected tropical diseases, 2023) Nambala, Peter; Mulindwa, Julius; Harry, Noyes; Alibu, Vincent Pius; Nerima, Barbara; Namulondo, Joyce; Nyangiri, Oscar; Matovu, Enock; Annette, MacLeod; Musaya, Janelisa
    T. b. rhodesiense is the causative agent of Rhodesian human African trypanosomiasis (r-HAT) in Malawi. Clinical presentation of r-HAT in Malawi varies between foci and differs from East African HAT clinical phenotypes. The purpose of this study was to gain more insights into the transcriptomic profiles of patients with early stage 1 and late stage 2 HAT disease in Malawi. Whole blood from individuals infected with T. b. rhodesiense was used for RNA-Seq. Control samples were from healthy trypanosome negative individuals matched on sex, age range, and disease foci. Illumina sequence FASTQ reads were aligned to the GRCh38 release 84 human genome sequence using HiSat2 and differential analysis was done in R Studio using the DESeq2 package. XGR, ExpressAnalyst and InnateDB algorithms were used for functional annotation and gene enrichment analysis of significant differentially expressed genes. RNA-seq was done on 23 r-HAT case samples and 28 healthy controls with 7 controls excluded for downstream analysis as outliers. A total of 4519 genes were significant differentially expressed (p adjusted <0.05) in individuals with early stage 1 r-HAT disease (n = 12) and 1824 genes in individuals with late stage 2 r-HAT disease (n = 11) compared to controls. Enrichment of innate immune response genes through neutrophil activation was identified in individuals with both early and late stages of the disease. Additionally, lipid metabolism genes were enriched in late stage 2 disease. We further identified uniquely upregulated genes (log2 Fold Change 1.4–2.0) in stage 1 (ZNF354C) and stage 2 (TCN1 and MAGI3) blood. Our data add to the current understanding of the human transcriptome profiles during T. b. rhodesiense infection. We further identified biological pathways and transcripts enriched than were enriched during stage 1 and stage 2 r-HAT. Lastly, we have identified transcripts which should be explored in future research whether they have potential of being used in combination with other markers for staging or r-HAT.
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    High prevalence of Schistosoma mansoni infection and stunting among school age children in communities along the Albert-Nile, Northern Uganda: A cross sectional study
    (PLoS neglected tropical diseases, 2022) Mulindwa, Julius; Namulondo, Joyce; Kitibwa, Anna; Nassuuna, Jacent; Asanya Nyangiri, Oscar; Kimuda, Magambo Phillip; Boobo, Alex; Nerima, Barbara; Busingye, Fred; Rowel, Candia; Namukuta, Annet; Ssenyonga, Ronald; Ukumu, Noah; Paul, Ajal; Adriko, Moses; Harry, Noyes; Claudia, J. de Dood; Paul, L. A. M. Corstjens
    Background Knowing the prevalence of schistosomiasis is key to informing programmes to control and eliminate the disease as a public health problem. It is also important to understand the impact of infection on child growth and development in order to allocate appropriate resources and effort to the control of the disease. Methods We conducted a survey to estimate the prevalence of schistosomiasis among school aged children in villages along the Albert-Nile shore line in the district of Pakwach, North Western Uganda. A total of 914 children aged between 10–15 years were screened for Schistosoma mansoni using the POC-CCA and Kato Katz (KK) techniques. The infection intensities were assessed by POC-CCA and KK as well as CAA tests. The KK intensities were also correlated with POC-CCA and with CAA intensity. Anthropometric measurements were also taken and multivariate analysis was carried out to investigate their association with infection status. Results The prevalence of schistosomiasis using the POC-CCA diagnostic test was estimated at 85% (95% CI: 83–87), being highest amongst children living closer to the Albert-Nile shoreline. Visual scoring of the POC-CCA results was more sensitive than the Kato Katz test and was positively correlated with the quantified infection intensities by the CAA test. The majority of the children were underweight (BMI<18.5), and most notably, boys had significantly lower height for age (stunting) than girls in the same age range (p < 0.0001), but this was not directly associated with S. mansoni infection. Conclusion High prevalence of S. mansoni infection in the region calls for more frequent mass drug administration with praziquantel. We observed high levels of stunting which was not associated with schistosomiasis. There is a need for improved nutrition among the children in the area.
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    The Lake Victoria Island Intervention Study on Worms and Allergy-related diseases (LaVIISWA): Study Protocol for a Randomised Controlled Trial
    (Trials, 2015) Nampijja, Margaret; Webb, Emily L.; Kaweesa, James; Kizindo, Robert; Namutebi, Milly; Nakazibwe, Esther; Oduru, Gloria; Kabuubi, Prossy; Kabagenyi, Joyce; Kizito, Dennison; Muhangi, Lawrence; Akello, Mirriam; Verweij, Jaco J.; Nerima, Barbara; Tukahebwa, Edridah; Elliott, Alison M.
    The Hygiene Hypothesis proposes that infection exposure protects against inflammatory conditions. Helminths possess allergen-like molecules and may specifically modulate allergy-related immunological pathways to inhibit responses which protect against them. Mass drug administration is recommended for helminth-endemic communities to control helminth-induced pathology, but may also result in increased rates of inflammation-mediated diseases in resource-poor settings. Immunological studies integrated with implementation of helminth control measures may elucidate how helminth elimination contributes to ongoing epidemics of inflammatory diseases. We present the design of the Lake Victoria Island Intervention Study on Worms and Allergy-related diseases (LaVIISWA), a cluster-randomised trial evaluating the risks and benefits of intensive versus standard anthelminthic treatment for allergy-related diseases and other health outcomes.
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    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.
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    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.
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    Transcriptome analysis of peripheral blood of Schistosoma Mansoni Infected Children from the Albert Nile Region in Uganda Reveals Genes Implicated in Fibrosis Pathology.
    (bioRxiv, 2023) Namulondo, Joyce; Nyangiri, Oscar Asanya; Kimuda, Magambo Phillip; Nambala, Peter; Nassuuna, Jacent; Egesa, Moses; Nerima, Barbara; Biryomumaisho, Savino; Nabukenya, Immaculate; Drago, Kato; Tweyongyere, Robert; Matovu, Enock; Mulindwa, Julius; Mugasa, Claire Mack
    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 and enriched pathways in differentially expressed genes (DEGs) were identified using REACTOME. 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.
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    Transcriptome profiling reveals genes associated with inflammation and fibrosis among 10 - 15-yearold children with Schistosoma mansoni and Plasmodium falciparum coinfection along the Albert Nile in Uganda
    (Research Square, 2024) Namulondo, Joyce; Nyangiri Oscar Asanya; Nyangiri, Magambo Phillip Kimuda; Nambala, Peter; Nassuuna, Jacent; Kabagenyi, Joyce; Egesa, Moses; Nerima, Barbara; Biryomumaisho, Savino; Mugasa, Claire Mack; Harry, Noyes; Tweyongyere, Robert; Matovu, Enock; Mulindwa, Julius
    Background: Malaria and schistosomiasis are significant parasitic diseases in Uganda and coinfections with the two are not uncommon in areas endemic to both parasites. The aim of this study was to determine the effect of P. falciparum and S. mansoni coinfection on the gene expression in peripheral blood of school age children aged between 10–15 years. Methods: A cross sectional study of children aged 10–15 years, was conducted in selected sites along the Albert Nile in Pakwach District in northwest Uganda. Quantitative PCR (qPCR) was used to test for S. mansoni and P. falciparum infection. Furthermore samples that were sequenced using Illumina NovaSeq S4 and the reads aligned to the GRCh38 human genome were matched with those with S. mansoni and P. falciparum qPCR results. Differential gene expression analysis was done using DESeq2. Results: Of the 210 study particpants, 76.2% (160/210) were P. falciparum positive, 91% (191/210) were S. mansoni positive and 150 (71%) had coinfection with both P. falciparum and S. mansoni, which was slightly fewer coinfections than expected by chance (Fisher exact test p-value of 0.02). RNAseq data was obtained for 33 participants of which 17 had P. falciparum and S. mansoni coinfection, 4 S. mansoni infection only, 1 had P. falciparum infection only while 11 were uninfected. Principal component analysis revealed clustering of gene expression by gender and infection status when S. mansoni and P. falciparum coinfected children were compared with uninfected children. We observed 15 DEGs of which 2 (CEPT1 and RETREG1) were downregulated and 13 (GAS6, DEXI, PALMD, SAMD15 AC138028.4, GFOD1-AS1, AC034102.6, AC005153.1, AC020914.1, AC017028.2, AC244502.3, AC013486.1, AC106760.1) upregulated when S. mansoni and P. falciparum coinfected children were compared with uninfected children. The differentially expressed genes are associated with inflammation and fibrosis and also included regulatory long noncoding RNA. 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. The study shows differential expression of genes associated with inflammation and fibrosis among coinfected when compared to the uninfected children.
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    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.