Transcriptomic Analysis of Schistosoma haematobium Adaptation to the Human Host: Implications for Drug Target Identification in Nigerian Isolates

Schistosoma haematobium adult worms establish a long-term infection in the human vesical venous plexus by deploying an array of molecular strategies to evade host immunity, and transcriptomic characterisation of these adaptations in Nigerian isolates offers a rich source of novel drug target candidates. This doctoral research performs comprehensive transcriptomic analysis of S. haematobium adult worms isolated from human patients in Kebbi State, North West Nigeria, to characterise host adaptation mechanisms and identify drug targets. Adult worms were recovered by perfusion of vesical venous plexus tissue from consenting patients undergoing surgical intervention for advanced bladder complications at Usmanu Danfodiyo University Teaching Hospital. Total RNA was extracted from male and female worms separately and subjected to RNA sequencing on the Illumina platform. Differential expression analysis between male and female worms, and between worms from treatment-naive and praziquantel-experienced patients, was performed using DESeq2. Transcripts encoding tegumental proteins, proteases, signalling molecules, and immune evasion factors were prioritised. Molecular docking of existing drug libraries against top-priority target structures was performed in silico. Evidence from 2020 to 2024 identifies Schistosoma tegumental proteins and signalling kinases as the most tractable drug targets, with several showing druggable pockets exploitable by FDA-approved scaffold compounds. This study produces the first RNA-seq dataset from Nigerian S. haematobium human isolates. Findings will be published in a high-impact parasitology journal and submitted to the WHO product development pipeline for tropical diseases. Keywords: Schistosoma haematobium, transcriptomics, drug targets, host adaptation, RNA sequencing.