Transcriptome profiling reveals genes associated with inflammation and fibrosis among 10 - 15-year-old children with Schistosoma mansoni and Plasmodium falciparum coinfection along the Albert Nile in Uganda

Abstract

<title>Abstract</title> <bold>Background</bold> 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 <italic>P. falciparum</italic> and <italic>S. mansoni</italic> coinfection on the gene expression in peripheral blood of school age children aged between 10–15 years.<bold>Methods</bold> 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 <italic>S. mansoni</italic> and <italic>P. falciparum</italic> infection. Furthermore samples that were sequenced using Illumina NovaSeq S4 and the reads aligned to the GRCh38 human genome were matched with those with <italic>S. mansoni</italic> and <italic>P. falciparum</italic> qPCR results. Differential gene expression analysis was done using DESeq2.<bold>Results</bold> Of the 210 study particpants, 76.2% (160/210) were <italic>P. falciparum</italic> positive, 91% (191/210) were <italic>S. mansoni</italic> positive and 150 (71%) had coinfection with both <italic>P. falciparum</italic> and <italic>S. mansoni</italic>, 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 <italic>P. falciparum</italic> and <italic>S. mansoni</italic> coinfection, 4 <italic>S. mansoni</italic> infection only, 1 had <italic>P. falciparum</italic> infection only while 11 were uninfected. Principal component analysis revealed clustering of gene expression by gender and infection status when <italic>S. mansoni</italic> and <italic>P. falciparum</italic> 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 <italic>S. mansoni</italic> and <italic>P. falciparum</italic> coinfected children were compared with uninfected children. The differentially expressed genes are associated with inflammation and fibrosis and also included regulatory long noncoding RNA.<bold>Conclusions</bold> By molecular detection, this study observed a high prevalence of <italic>P. falciparum</italic> among the school age children (10–15 years) living in the <italic>S. mansoni</italic> 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.