Differential gene expression in Schistosoma mansoni infected children along Lake Albert in uganda

Abstract

Over 290 million people are infected by schistosomes worldwide. A third of Uganda’s population is infected and these are along freshwater bodies. Knowing the prevalence of schistosomiasis is key to informing national control programs with the goal of eliminating the disease as a public health problem. Schistosoma mansoni (S. mansoni) infection is known to modulate immune responses and has been shown to influence response to coinfections, their treatment as well as to vaccination. Coinfections of Schistosoma and plasmodium are not uncommon in areas endemic to both parasites. S. mansoni infection has been shown to influence malaria clinical presentation.

A survey to estimate the prevalence of schistosomiasis among school aged children in villages along the Albert-Nile shoreline in the district of Pakwach, Northwestern Uganda was conducted.Point of care circulating cathodic antigen (POC-CCA) and Kato Katz (KK) technique were used for screening children 10 -15 years. Additionally, RNA extracted from peripheral blood collected from 44 S. mansoni infected (34 high and 10 low by 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. Finally, the CAA test and quantitative PCR (qPCR) were used to test for S. mansoni infection intensity and the latter used to test for presence and intensity P. falciparum infection. DESeq2 analysis to identify differentially expressed genes among these children.

The overall prevalence of schistosomiasis using the Antigen POC-CCA diagnostic test was estimated at 85% (95% CI: 83 - 87), being highest amongst children living closer to the Albert-Nile shoreline. Fourteen (14) differentially expressed genes (DEGs) between S. mansoni infected and uninfected individuals. Fifteen (15) differentially expressed genes were significant of which 13 were upregulated and 2 were downregulated. The DEGs identified were associated with inflammation and fibrosis.

There was a high prevalence of S. mansoni infection in the region which calls for more frequent mass drug administration with Praziquantel. The RNAseq data suggest expression of fibrosis associated genes as well as genes that regulate fibrosis in S. mansoni infection, as a possible adaptation to infection. Molecular testing by quantitative PCR demonstrated 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 also showed differential expression of genes associated with inflammation and fibrosis among children with P. falciparum and S. mansoni coinfection.