Monkeypox Virus Infections in Humans

Abstract

Human monkeypox is a viral zoonosis endemic to West and Central Africa that has recently generated increased interest and concern on a global scale as an emerging infectious disease threat in the midst of the slowly relenting COVID-2019 disease pandemic. The hallmark of infection is the development of a flu-like prodrome followed by the appearance of a smallpox-like exanthem. Precipitous person-to-person transmission of the virus among residents of 100 countries where it is nonendemic has motivated the immediate and widespread implementation of public health countermeasures. In this review, we discuss the origins and virology of monkeypox virus, its link with smallpox eradication, its record of causing outbreaks of human disease in regions where it is endemic in wildlife, its association with outbreaks in areas where it is nonendemic, the clinical manifestations of disease, laboratory diagnostic methods, case management, public health interventions, and future directions.

Keywords: Monkeypox virus; Orthopoxvirus; immunization; monkeypox; outbreak; public health; tecovirimat; virology.

FIG 1

(A) Gambian giant rat (Cricetomys gambianus). (Reproduced from https://commons.wikimedia.org/wiki/File:Cricetomys_gambianus_Gambian_giant_Rat-1914404.jpg, by K. Paulick, available under the Creative Commons CC0 1.0 Universal Public Domain Dedication.) (B) Congo rope squirrel (Funisciurus congicus). (Reproduced from https://commons.wikimedia.org/wiki/File:Congo_rope_squirrel_%28Funisciurus_congicus%29.jpg, by C. J. Sharp, licensed under the Creative Commons Attribution-Share Alike 4.0 International license.) (C) Red-legged sun squirrel (Heliosciurus rufobrachium). (Reproduced from https://commons.wikimedia.org/wiki/File:Red-legged_sun_squirrel_%28Heliosciurus_rufobrachium%29_2.jpg, by C. J. Sharp, licensed under the Creative Commons Attribution-Share Alike 4.0 International license.)

FIG 2

Clade-based geographic distribution of locally acquired or imported human monkeypox virus infections in African countries (yellow, clade I, formerly known as the Central African clade; red, clade II, formerly known as the West African clade; green, clades I and II). Only imported cases have been reported in Benin. In Ghana, no human cases have been reported, although clade II is endemic among terrestrial rodents in that country. CAR, Central African Republic; DRC, Democratic Republic of the Congo. (Adapted from https://commons.wikimedia.org/wiki/File:Africa_location_map_without_rivers.svg, by Eric Gaba, available under the terms of the GNU Free Documentation license, version 1.2.)

FIG 3

Pathogenesis of monkeypox virus (38, 42, 45, 72–74, 76, 77).

FIG 4

(A) Exanthem of monkeypox virus infection in humans. Vesicles and pustules (A, D, and H), macules (B and C), subungual lesions (F and G), and an ultrasonographic image of an abscess are shown. (The images are reproduced from reference , which was published under a Creative Commons BY-NC-ND 4.0 license.) (B) Nonsynchronous onset and progression of monkeypox skin lesions on the face, hands, and genitals (112). (The images are reproduced from https://commons.wikimedia.org/wiki/File:Monkeypox_lesion_progression.jpg, licensed under the Creative Commons Attribution 4.0 International license.)

FIG 5

Prairie dog. (Reproduced from https://commons.wikimedia.org/wiki/File:Prairie_Dog_%2819014508183%29.jpg, by W. Warby, licensed under the Creative Commons Attribution 2.0 Generic license.)

FIG 6

Chemical structures of cidofovir, brincidofovir, and tecovirimat. (Reproduced from https://commons.wikimedia.org/wiki/File:Cidofovir.svg, by Artur [username Ijfa-ag] [cidofovir], and from https://commons.wikimedia.org/wiki/File:Brincidofovir.svg [brincidofovir] and https://commons.wikimedia.org/wiki/File:Tecovirimat.svg [tecovirimat], by Ed [username Edgar181], all available under the Creative Commons CC0 1.0 Universal Public Domain Dedication.)

FIG 7

Mechanism of action of tecovirimat in a human cell infected with monkeypox virus (223, 225, 231–234, 249). IV, immature virus; IMV, intracellular mature virus; IEV, intracellular enveloped virus; EEV, extracellular enveloped virus; ER, endoplasmic reticulum.