One in Five Mpox Patients May Also Carry Varicella Zoster Virus, Review Finds

A new systematic review and meta-analysis published in BMC Infectious Diseases has brought together the scattered evidence on simultaneous infection with mpox virus and varicella zoster virus, the agent responsible for chickenpox and shingles. The analysis, led by Amirvala Keyhani and colleagues at AJA University of Medical Sciences in Tehran, concludes that roughly one in five patients diagnosed with mpox in the study populations examined also showed evidence of varicella zoster virus coinfection. The finding, drawn from twelve eligible studies conducted across five countries, carries significant weight for clinicians who must distinguish between two viral diseases that can produce strikingly similar skin lesions, and for public health authorities designing surveillance systems in regions where both pathogens circulate.

The research team followed the PRISMA guidelines for systematic reviews, searching six major databases: PubMed, Scopus, Web of Science, EMBASE, Google Scholar, and the Cochrane Library. Their search covered studies published between January 2000 and October 2024, a window that spans both the long-standing endemic transmission of mpox in parts of Central and West Africa and the dramatic 2022 global outbreak that spread the virus far beyond its traditional range. From 860 records initially identified, only twelve studies met the inclusion criteria, reporting data from the Democratic Republic of Congo, Nigeria, Brazil, the Central African Republic, and Pakistan. That modest number of qualifying studies is itself telling, reflecting how rarely clinicians and researchers have systematically looked for dual infection even when both viruses are present in the same community.

The pooled prevalence of mpox and varicella zoster virus coinfection across the included study populations was 21.3 percent, with a 95 percent confidence interval of 15.0 to 29.4 percent. The statistical test for the overall effect yielded a Z value of 5.93 and a P value below 0.001, indicating that the pooled estimate is unlikely to be a chance artifact. Yet the authors are careful to emphasize that this headline figure conceals enormous variability between studies. The I² statistic, which quantifies the proportion of variation attributable to genuine heterogeneity rather than sampling error, reached 93.6 percent, a level conventionally regarded as substantial. In practical terms, individual studies reported coinfection rates that differed widely depending on where and how the data were collected.

To probe that variability, the researchers conducted a series of sensitivity analyses, removing studies one at a time or applying alternative analytical assumptions to see whether the pooled estimate would shift. The event rates in these analyses ranged from 17.8 percent to 27.2 percent, with heterogeneity remaining at 93.6 percent throughout. The stability of the estimate within that band suggests the overall finding is not driven by any single outlier study, but the persistence of high heterogeneity means the pooled prevalence should be treated as an approximate summary rather than a precise universal rate. The authors also examined small-study effects, which can signal publication bias, using Egger’s regression, Begg’s test, and visual inspection of funnel plots. Both statistical tests were non-significant, but with only twelve studies in the pool, the power to detect bias was limited, and the researchers explicitly note that publication bias could not be excluded.

Subgroup analyses added a further layer of nuance. The team compared pooled prevalence between endemic settings, where mpox has circulated for decades, and non-endemic settings where the virus arrived more recently. They also compared studies conducted before 2022 with those from the 2022 outbreak period. Neither comparison reached statistical significance: the test for differences between subgroups produced a Q-between P value of 0.907 for region of residence and 0.132 for study period. In other words, the proportion of mpox patients with concurrent varicella zoster virus infection appeared broadly similar whether the data came from African endemic regions or from newer outbreak settings, and whether the infections occurred before or during the global epidemic. This consistency, if it holds up as more data accumulate, suggests that the biological or epidemiological factors driving coinfection are not confined to any single geographic or temporal context.

The clinical rationale for studying this particular pairing is rooted in the overlapping presentation of the two diseases. Mpox, caused by the monkeypox virus, and varicella, caused by varicella zoster virus, both produce febrile illness followed by a disseminated vesicular rash. In their early stages, the lesions of the two conditions can look deceptively alike, and in a patient presenting with fever and a spreading blistering eruption, a clinician in an endemic area may face genuine diagnostic uncertainty. Polymerase chain reaction testing can distinguish the viruses definitively, but such testing is not uniformly available in the resource-limited settings where mpox has historically been most common. When coinfection occurs, the diagnostic challenge intensifies: a patient may be treated for one disease while the other goes unrecognized, potentially affecting clinical management, infection control decisions, and contact tracing.

The public health implications extend beyond the bedside. If a fifth of mpox cases in some populations also involve varicella zoster virus, then surveillance systems that rely on clinical diagnosis alone may systematically misclassify cases, and vaccination strategies may need to account for the interaction. The authors call for improved differential diagnostics, integrated surveillance that tests for both pathogens, greater clinician awareness, and targeted public health interventions, particularly in endemic settings where both viruses co-circulate and diagnostic infrastructure is often weakest. They also highlight a specific gap in the current evidence base: the included studies generally did not distinguish between primary varicella infection, in which a person encounters varicella zoster virus for the first time, and reactivation of latent virus as shingles, which can occur when immune defenses wane. These are biologically distinct scenarios with different implications, and disentangling them is a priority for future research.

Methodological rigor was addressed through the Appraisal tool for Cross-Sectional Studies, known as AXIS, which the team used to assess the quality of the included research. The meta-analysis employed a random-effects model, the standard choice when heterogeneity is high, since it does not assume that all studies estimate a single true effect but instead models a distribution of effects across study contexts. Cochran’s Q test was used alongside the I² statistic to evaluate heterogeneity formally. The study received no external funding; the Central Research Laboratory of AJA University of Medical Sciences provided institutional resources, and the authors declared no competing interests. The work is published open access under a Creative Commons Attribution 4.0 license, making the full dataset and analysis available to researchers worldwide.

The limitations of the evidence base deserve emphasis. Twelve studies from five countries represent a thin foundation for a global estimate, and the geographic coverage is heavily weighted toward regions where mpox was already recognized before 2022. The authors themselves caution that the one-in-five figure should be interpreted cautiously given the substantial heterogeneity and the restricted geographic scope of the underlying data. Different study designs, different diagnostic approaches, and different patient populations all contributed to the spread of observed prevalence rates, and the meta-analysis cannot fully separate these sources of variation. Moreover, because the search window closed in October 2024, the analysis captures only the early phase of sustained mpox transmission in non-endemic countries, leaving open the question of whether coinfection patterns will shift as the virus establishes itself in new populations with different varicella vaccination coverage and different age structures.

Even with these caveats, the study marks an important step in a neglected corner of viral epidemiology. The 2022 mpox outbreak demonstrated how quickly a previously localized orthopoxvirus can become a global concern, and it exposed how little systematic data exist on how mpox interacts with other common human pathogens. Varicella zoster virus is among the most widespread herpesviruses, infecting most people worldwide during childhood or adolescence and then persisting latently in sensory ganglia for life. Understanding how frequently it coincides with mpox infection, whether the two viruses influence each other’s severity, and whether coinfection worsens outcomes are questions with direct consequences for patient care. The authors’ recommendation that future work distinguish primary varicella from reactivation is particularly important, because the immunological context of the two scenarios differs fundamentally. For now, the message for clinicians is clear: in a patient with a vesicular rash consistent with mpox, varicella zoster virus should remain on the differential, and laboratory confirmation of both pathogens should be pursued wherever testing capacity allows.

Subject of Research: Epidemiology and clinical implications of mpox and varicella zoster virus coinfection

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

Article References: Mpox and Varicella Zoster Virus coinfection in endemic and outbreak settings: a systematic review and meta-analysis. (n.d.). https://doi.org/10.1186/s12879-026-14622-7

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14622-7

Keywords: mpox, monkeypox virus, varicella zoster virus, coinfection, systematic review, meta-analysis, prevalence, epidemiology, diagnostics, public health, surveillance, BMC Infectious Diseases