Integrated Epidemiological, Clinical, and Molecular Evidence Points to An Earlier Origin of the Current Monkeypox Outbreak and a Complex Route of Exposure

Abstract

Concurring evidence from multiple sources (epidemiology, genetics/genomics, clinical virology, and global public health) points to complex, non-linear pathogenesis of the current outbreak dynamics: a “long and winding road”, in which several factors may have contributed to shaping the macro- (divergence) and micro-evolutionary (sub-clustering) story and trajectory of the infectious agent, ranging from the cessation of smallpox vaccination, the waning of immunity conferred by the vaccine, animal trade, zoonotic spillovers to new animal reservoirs and hosts in new niches of expansion, emerging epizootic events, international travel, and spread across particular social networks, characterized by patterns of high frequencies of close contacts, such as the men having sex with men (MSM) community, with super spreader events linked to use of saunas and other venues for sexual encounters and gathering events/festivals (like those at Maspalomas, Spain, and Antwerp, Belgium). However, if evidence of multiple transmission chains, some of which “cryptic” and undetected, is accumulating, precise mechanisms underlying the “complex route of monkeypox exposure” have still to be elucidated.

Note:
Funding Information: NLB and JDK acknowledge support from IDRC (Grant No. 109981). JDK acknowledges support from New Frontier in Research Fund-Exploratory (Grant No. NFRFE-2021- 00879) and NSERC Discovery Grant (Grant No. RGPIN-2022-04559).

Conflict of Interests: No conflict of interest declared.