Monkeypox (Mpox), a zoonotic disease caused by the monkeypox virus, has gained global attention due to rising incidence and the emergence of new clades. Understanding the epidemiology, transmission dynamics, and diagnostic challenges associated with the two major clades, Clades I and II, is crucial for outbreak preparedness and control. This review analyzes Mpox clades, highlighting their geographic distribution, virulence, transmissibility, and diagnostic approaches. It also presents recent outbreaks, diagnostic advancements, vaccination strategies, and critical research gaps in Mpox surveillance and response. Clade I, primarily in Central Africa, exhibits the highest virulence with a 5–10% case fatality rate. Clade II, which includes subclades IIa, IIb, and the newly identified Clade Ib, demonstrates lower virulence but higher transmissibility beyond endemic regions. Recent outbreaks (2022–2024), driven by Clade IIb, present atypical clinical presentations and emphasize intimate human-to-human contact as a key transmission route. Polymerase chain reaction, next-generation sequencing, and emerging CRISPR-based diagnostics have improved detection, while modified vaccinia Ankara-based vaccines have shown effectiveness despite challenges in equitable distribution. Addressing critical research gaps, such as clade-specific virulence mechanisms, zoonotic reservoirs, and evolutionary patterns, is essential for improving Mpox surveillance and control. Strengthening genomic surveillance, expanding access to affordable diagnostics, and fostering international collaboration will enhance preparedness for future outbreaks and mitigate the impact of this emerging infectious disease. • Comparison of Mpox virus (MPXV) clades, in geography, virulence, transmission, and clinical outcomes between Clade I, Clade II, and emerging subclades IIb and Ib. • The epidemiology of Mpox focuses on the 2022–2024 global outbreaks of Clade IIb, marked by unusual clinical presentations and fast human-to-human spread in non-endemic areas. • Key advancements in diagnostic technologies like PCR, NGS, and CRISPR assays, improving MPXV detection and clade differentiation. • The effectiveness of MVA-based vaccines against various MPXV clades is presented while highlighting challenges in equitable distribution and region-specific vaccination strategies. • Emerging Mpox research priorities include genomic surveillance, clade-specific virulence, affordable diagnostics, and overcoming socioeconomic barriers to outbreak management.
Srivastava et al. (2025) studied this question.