Monkeypox: A Comprehensive Review

Abstract

The 2022 multi-country monkeypox outbreak in humans has brought new public health adversity on top of the ongoing coronavirus disease 2019 (COVID-19) pandemic. The disease has spread to 104 countries throughout six continents of the world, with the highest burden in North America and Europe. The etiologic agent, monkeypox virus (MPXV), has been known since 1959 after isolation from infected monkeys, and virulence among humans has been reported since the 1970s, mainly in endemic countries in West and Central Africa. However, the disease has re-emerged in 2022 at an unprecedented pace, with particular concern on its human-to-human transmissibility and community spread in non-endemic regions. As a mitigation effort, healthcare workers, public health policymakers, and the general public worldwide need to be well-informed on this relatively neglected viral disease. Here, we provide a comprehensive and up-to-date overview of monkeypox, including the following aspects: epidemiology, etiology, pathogenesis, clinical features, diagnosis, and management. In addition, the current review discusses the preventive and control measures, the latest vaccine developments, and the future research areas in this re-emerging viral disease that was declared as a public health emergency of international concern.

Keywords: emergency; emerging viral infectious diseases; epidemic; international concern; prevention; public health; vaccination; zoonosis.

Figure 1

The total number of confirmed monkeypox cases per country. Data are based on (OurWorldInData.org, accessed on 9 September 2022) as reported by the end of May, June, July, and August 2022 [18].

Figure 2

Negative-stained transmission electron micrograph of M-type MPXV particle (A). Thin section of viral particles on skin sample, showing ovoid mature virions on the left and spherical immature virions on the right. Micrographs are courtesy of the Centers for Disease Control and Prevention (CDC) Public Health Image Library (PHIL) [28] (B). Schematic representation of MPXV virion structure (C).

Figure 3

Unrooted phylogenetic tree of MPXV genomes from 219 isolates sampled from 1970–2022 using iqtree2, aligned to reference (NC_063383) at the 3′ inverted terminal repeat (ITR) region using Geneious Prime. The tree shows the recently proposed three-clade classifications, consisting of Clade 1 (previously known as Congo Basin/Central Africa), Clade 2 (Western Africa), and Clade 3 (strong evidence of human-to-human transmission of MPXV (hMPXV)).

Figure 4

As a member of pattern recognition receptors (PRRs), TLR plays a critical role in recognizing various noxious molecules. Upon its interaction with those molecules, the cytoplasmic domain (TIR) of TLR recruits the appropriate adaptor proteins (e.g., MyD88, TRIF, or TRAM). This interaction induces the subsequent molecular pathways that will eventually upregulate the expression of NF-κB, which is critical in modulating the innate immune system. It has been found that this mechanism can be impaired by the action of a MPXV protein called A47R. This viral protein can interact with the adaptor proteins leading to the impairment of viral recognition by the immune system. TLR (Toll-like receptor); TIR (Toll/interleukin-1 receptor); MyD88 (myeloid differentiation primary-response gene 88); TRIF (TIR-domain-containing adaptor protein inducing IFNβ); TRAM (TRIF-related adaptor molecule); NF-κB (nuclear factor kappa B). The figure was created by Biorender.

Figure 5

The clinical and laboratory features of monkeypox. BUN: blood urea nitrogen. The figure was created by Biorender.

Figure 6

Schematic overview of the monkeypox virus life cycle and the mechanism of action of anti-poxvirus drugs. Like all poxviruses, monkeypox replicates in the cytoplasm of infected cells. Cidofovir and brincidofovir inhibit viral DNA polymerase; tecovirimat and NIOCH-14 prevents the formation of the cell-associated enveloped virion (CEV) and extracellular enveloped virion (EEV); and VIG prevents virion to infect new cells. The figure was created by Biorender.