Mpox and Varicella Zoster Virus coinfection in endemic and outbreak settings: a systematic review and meta-analysis

Abstract

Abstract Background MPOX-VZV co-infection poses diagnostic challenges and public health implications due to the overlap in clinical presentation and complications. Evidence on the epidemiology and clinical outcomes of MPOX-VZV co-infection remains limited. This systematic review and meta-analysis summarize the available epidemiological evidence and discusses the associated diagnostic and public health implications. Methods A systematic and comprehensive literature search was performed in PubMed, Scopus, Web of Science, EMBASE, Google Scholar, and the Cochrane Library for studies published between January 2000 and October 2024, following PRISMA guidelines. We included studies that reported MPOX–VZV coinfection prevalence. Standard methods were used for data extraction and meta-analysis, and methodological quality was assessed using the Appraisal tool for Cross-Sectional Studies (AXIS). The pooled prevalence was derived from a random-effects meta-analysis; heterogeneity was evaluated with Cochran’s Q and I² statistics. Sensitivity analysis and tests for small-study effects were also performed (Egger’s regression, Begg’s test, and funnel plots). Subgroup analyses by region of residence and study period were also performed using the random-effects model. Results Of the 860 records identified, 12 studies were eligible for inclusion, with data from the Democratic Republic of Congo, Nigeria, Brazil, Central African Republic, and Pakistan. The pooled prevalence across the included study populations was 21.3% (95% CI: 15.0–29.4%, Z = 5.93, P < 0.001). There was substantial heterogeneity (I²=93.6%), and event rates varied by region, study design, and diagnostic approach. The sensitivity analyses showed event rates ranging from 17.8% to 27.2% (I²=93.6%). Egger’s and Begg’s tests were non-significant; however, with only 12 studies, publication bias could not be excluded. Subgroup analyses showed comparable pooled prevalence between endemic and non-endemic settings and between the pre-2022 and 2022-outbreak periods, with neither region of residence nor study period reaching statistical significance as a moderator of prevalence (Q-between p = 0.907 and p = 0.132, respectively). Conclusions In the included study populations, MPOX–VZV coinfection was observed in approximately one in five patients with mpox, but this estimate should be interpreted cautiously because of substantial heterogeneity and limited geographic coverage. Improved differential diagnostics, integrated surveillance, clinician awareness, and targeted public health interventions are recommended, particularly in endemic settings. Future research should clarify the epidemiology and clinical significance of coinfection and distinguish primary varicella from VZV reactivation.