An urgent need for diagnostic tools to address global mpox public health emergencies.

Monkeypox virus (MPXV) is the causative agent of mpox, a zoonosis formerly known as monkeypox. MPXV can be divided into clades I and II, which are further divided into subclades Ia, Ib, IIa, and IIb. Since May 2022, subclade IIb MPXV has rapidly spread outside Africa to more than 100 countries due to increased human-to-human transmission. Clade I is a more virulent MPXV endemic in Central Africa with up to 10% mortality in humans. Clade I has recently evolved into a novel subclade Ib and caused outbreaks in non-endemic neighboring countries and other continents. In response to mpox, the World Health Organization has declared Public Health Emergencies of International Concern in July 2022 (subclade IIb) and August 2024 (subclade Ib). The emergence and spread of the more virulent subclade Ib MPXV has caused a significant global public health threat, particularly in low- and middle-income countries (LMICs). The evolution of MPXV has outpaced the development of novel diagnostic assays, hampering the global response. There is an urgent need for additional diagnostic tools for the detection and surveillance of MPXV, especially subclade Ib MPXV, in LMICs. Herein, we provide the current epidemiology of mpox, analyze the diagnostic gaps for mpox, and evaluate the potential of additional detection strategies to be added to the suite of mpox assays. This commentary not only sheds light on the currently available diagnostic tools for mpox but also highlights the urgent need for additional diagnostic tools in response to the new global mpox public health threats.