Targeted Metagenomics Reveals Hidden Chickenpox Epidemic Amid Mpox Surveillance in Uganda

In this study, we investigated clinically suspected Mpox cases that tested negative for MPXV by PCR. Using metagenomic sequencing, we identified VZV as the predominant pathogen among these cases. To facilitate detailed genomic characterization of VZV, we developed a custom analysis pipeline, VaricellaGen (https://github.com/MicroBioGenoHub/VaricellaGen), an automated pipeline that integrates multiple bioinformatics tools for quality control, variant calling, consensus genome generation, clade typing, and phylogenetic analysis. Our findings highlight the pivotal role of genomics in outbreak investigations, demonstrating how high-throughput sequencing and advanced bioinformatics can resolve diagnostic ambiguities, leading to more accurate pathogen identification and more effective public health responses.