Targeted metagenomics reveals hidden chickenpox epidemic amid Mpox surveillance in Uganda

In regions where both monkeypox virus (MPXV) and varicella zoster virus (VZV) are co-circulating, overlapping clinical manifestations can complicate clinical diagnosis. During the MPXV outbreak declared in Uganda in July, 2024, symptomatic suspected cases tested PCR negative for Mpox. To determine the cause of symptoms, we employed metagenomic sequencing with a targeted Viral Surveillance panel in 284 MPXV negative samples. VZV was identified as the predominant pathogen in 86% of MPXV-negative cases, suggesting a concurrent chickenpox surge. Using the VaricellaGen pipeline for variant calling, clade typing, and phylogeny, 118 (49%) samples that achieved ≥ 70% genome coverage were of clade 5 based on the single-nucleotide polymorphism (SNP) dataset. This data confirms co-circulation of VZV during the MPXV outbreak in Uganda. Our results underscore the need for laboratory confirmation of MPXV and the inclusion of VZV in the testing algorithm during the Mpox outbreak.