Rethinking mpox: epidemiology, clinical variants, diagnosis, and response

Monkeypox disease, now commonly referred to as mpox, was once considered a geographically restricted zoonotic disease but has emerged as a global public health concern. The 2022 multinational outbreak marked a turning point, with notable shifts in transmission dynamics, affected populations, and clinical manifestations. Classical cases typically involve fever, lymphadenopathy, and a centrifugal vesiculopustular rash; however, recent outbreaks have revealed atypical presentations, including genital and perianal lesions, minimal or absent prodromal symptoms, and asynchronous rash evolution. These variations have complicated early clinical recognition and may contribute to delayed diagnosis and onward transmission. This review synthesizes current evidence on the evolving epidemiology of mpox, highlights differences between endemic and non-endemic outbreaks, and describes the full spectrum of typical and atypical clinical features. It also assesses diagnostic approaches, including molecular and point-of-care techniques, and evaluates the efficacy and limitations of current and emerging vaccines, such as JYNNEOS and ACAM2000. Future priorities include improving global surveillance, refining case definitions, expanding diagnostic access, and ensuring equitable vaccine distribution. Understanding the expanding clinical and epidemiological profile of mpox is essential for timely diagnosis, containment, and preparedness against future outbreaks.