The Re-Emergence of Mpox: Old Illness, Modern Challenges

Abstract

The Mpox virus (MPXV) is known to cause zoonotic disease in humans. The virus belongs to the genus Orthopoxvirus, of the family Poxviridae, and was first reported in monkeys in 1959 in Denmark and in humans in 1970 in the Congo. MPXV first appeared in the U.S. in 2003, re-emerged in 2017, and spread globally within a few years. Wild African rodents are thought to be the reservoir of MPXV. The exotic trade of animals and international travel can contribute to the spread of the Mpox virus. A phylogenetic analysis of MPXV revealed two distinct clades (Central African clade and West African clade). The smallpox vaccine shows cross-protection against MPXV infections in humans. Those who have not previously been exposed to Orthopoxvirus infections are more vulnerable to MPXV infections. Clinical manifestations in humans include fever, muscle pain, headache, and vesicle formation on the skin of infected individuals. Pathognomonic lesions include ballooning degenerations with Guarnieri-like inclusions in vesicular epithelial cells. Alterations in viral genome through genetic mutations might favor the re-emergence of a version of MPXV with enhanced virulence. As of November 2023, 92,783 cases and 171 deaths have been reported in 116 countries, representing a global public health concern. Here, we provide insights on the re-emergence of MPXV in humans. This review covers the origin, emergence, re-emergence, transmission, pathology, diagnosis, control measures, and immunomodulation of the virus, as well as clinical manifestations. Concerted efforts of health professionals and scientists are needed to prevent the disease and stop its transmission in vulnerable populations.

Keywords: MPXV; Mpox; emergence; wild rodents; zoonosis.

Figure 1

Classification of poxviruses, of the family Poxviridae. The Mpox virus belongs to the sub-family Chordopoxvirinae, of the genus Orthopoxvirus.

Figure 2

Distinctions between the Mpox virus (MPXV; Zaire-96 strain) and the variola virus (VARV; Kuwait-1967 strain) of the genus Orthopoxvirus. C3L, C10L K3L, E3L, and A49R loci are present in VARV but absent in MPXV. Moreover, MPXV has 10.5× longer ITRs with extra coding sequences and 11,000 longer nucleotide genomes with 4 extra genes. ITR: inverted terminal repeats; D14L: ortholog of the C3L gene; C3L: virulence-associated gene; C10L: gene coding IL-1B antagonist protein; K3L: interferon resistance gene; E3L: interferon resistance gene; A49R: gene coding phospho-transferase protein.

Figure 3

Transmission of Mpox. Schematic illustration to show the different routes of transmission. In (A), the numbers correspond to the following animals: 1. rope squirrel; 2. sooty mangabey; 3. prairie dog; 4. Gambian pouched rat; 5. African dormice rodent; 6. African giant pouched rat; 7. sun squirrel; 8. rufous-nosed rat; and 9. elephant shrew. (B) represents bush meat. In (C), the numbers correspond to the following: 1. skin crust; 2. patients’ used materials; 3. contaminated saliva; and 4. fecal materials. (D) represents transplacental transmission. (E) reflects hospital-borne infection. (F) shows transmission by respiratory droplets and direct contact. (G) shows sharing of 1. bed; 2. food; 3. a glass and other utensils; and 4. hand towels.

Figure 4

Clinical manifestations of Mpox infections in humans.