Genomic evidence of varicella-zoster virus among Mpox-suspected cases in Ethiopia during the 2022 Mpox multi-country outbreak

Chickenpox is a highly contagious viral infection caused by varicella-zoster virus (VZV) whose clinical manifestations mimic mpox posing challenges for diagnosis without laboratory confirmation. Here, we investigated VZV among the mpox-suspected cases, May to October 2022, in Ethiopia. Samples were collected from 202 mpox-suspected cases in 11 of Ethiopia's 14 regions and screened for mpox virus by real-time polymerase chain reaction (RT-PCR). Then, differential testing of other selected orthopoxviruses, VZV and herpes simplex virus (HSV) were conducted for 133 randomly selected samples. Whole-genome sequencing (WGS) and downstream analysis was performed on 8 VZV-positive samples. Descriptive statistics were used to summarize epidemiological and clinical data. All the 202 enrolled cases tested negative for mpox. Of these, 133 samples were tested for VZV, and 107 (80.5%, 95% CI: 72.9% - 86.3%) turned positive but remained negative for HSV and other tested orthopoxviruses. At least one VZV-positive case was reported in each region sampled. Half (49.6%) of the cases were hospitalized, with no fatalities. The sequences were clustered primarily in Clade 5 (62.5%, 5) followed by Clade 3 (25.0%, 2) and Clade 1 (12.5%, 1). This investigation confirmed VZV as the predominant causative agent among mpox-suspected cases. To our knowledge, this represents the first clade-level genomic characterization of VZV from Ethiopia, revealing circulation of multiple clades among samples collected during May to October 2022. The findings highlight the need to strengthen differential diagnostic capacities including multiplex testing, and building genomic surveillance capacities for epidemic intelligence and outbreak response.