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Smallpox
Published in Scott M. Jackson, Skin Disease and the History of Dermatology, 2023
Following leprosy, plague, and syphilis, smallpox is the last of the four major historical diseases with dermatologic implications to be discussed, and it was the deadliest and most dreadful of them all. Unlike the three previously described infections, which were caused by bacteria, smallpox is caused by a virus, that lifeless matter consisting of genetic material surrounded by protein that hijacks living cells to clone and disperse itself. The viruses responsible for smallpox are relatively large and known as Variola major and Variola minor and belong to the orthopoxvirus genus of DNA viruses that also includes cowpox. Variola minor was responsible for a less common and less deadly form of smallpox known as alastrim; our attention is focused on Variola major.
The Smallpox Story
Published in Rae-Ellen W. Kavey, Allison B. Kavey, Viral Pandemics, 2020
Rae-Ellen W. Kavey, Allison B. Kavey
With the advent of electron microscopy and molecular genetics, Variola was seen to be a very large, brick-shaped virus.40 In 1940, the viral genome was demonstrated to contain DNA, and subsequently, this was shown to be a single linear, double-stranded DNA genome of 186 kilobase pairs with a hairpin loop at each end connecting the two DNA strands.39 The DNA is bound to proteins in a nucleoprotein complex called the core, shaped like a dumbbell in the center of the virus, surrounded by a lipid and protein membrane (see Figure 2.1). The pox virion is the largest of all virions and its genetic material is among the largest of all viral genomes. The highly accurate poxviral DNA polymerase has conserved the sequences of these genes among all orthopoxviruses. Genes in the central region encode proteins involved in replication and virion structure while the flanking areas contain genes encoding proteins that modify the intra- and extracellular environment to favor viral replication and spread.42
Chemical and Biological Threats to Public Safety
Published in Frank A. Barile, Barile’s Clinical Toxicology, 2019
Naturally occurring smallpox (variola major) is a member of the orthopoxvirus family, the largest and most complex family of viruses. It is easily transmissible via close person-to-person contact. The virus accounted for 7% to 12% of all deaths in eighteenth-century England. The last case of smallpox in the United States occurred in 1949 and the last case in the world, in Somalia, in 1977. Routine vaccination in the United States was stopped in 1971; the World Health Organization (WHO) determined in 1980 that smallpox had been successfully eradicated from the world.
An HIV-positive man with painless ulcer and pustules: mpox, syphilis, or both?
Published in Baylor University Medical Center Proceedings, 2023
Ian Thien Bui, Benjamin Sloan, Marc Tribble, Angela Yen Moore
Mpox is diagnosed via vigorous swabbing of the suspected lesions for PCR testing for orthopoxvirus DNA. It is recommended to take two different swabs from each specimen. In patients with cutaneous manifestations, a throat swab may be performed to measure viral DNA but is not necessary in confirming the diagnosis. Per guidelines of the Centers for Disease Control and Prevention, if an orthopoxvirus PCR is positive, that meets sufficient criteria for a “probable” diagnosis of mpox. Negative, positive, and equivocal results should be reported first to state, tribal, local, or territorial health departments, such as the Dallas County Health and Human Services Department in this case.8 Pathology reveals ballooning degeneration, acanthosis, spongiosis, keratinocyte necrosis, multinucleated syncytial keratinocytes, and epidermal intracytoplasmic inclusions consistent with Guarneri bodies, along with superficial and deep perivascular and lichenoid infiltrate.1
Comparative evaluation of the clinical presentation and epidemiology of the 2022 and previous Mpox outbreaks: a rapid review and meta-analysis
Published in Infectious Diseases, 2023
George N. Okoli, Paul Van Caeseele, Nicole Askin, Ahmed M. Abou-Setta
Mpox has an estimated incubation period ranging from 5 to 21 d [12], with symptoms lasting from 2 to 4 weeks [13], during which an infected person can transmit disease. Some may be infected, but have no symptoms. The estimated mean serial interval for Mpox (the time from illness onset in a primary case to illness onset in the secondary case) is 9.8 d, ranging from 5.9 to 21.4 d [14], with the longest chain of transmission in a community during the 2022 outbreaks estimated to be 6 to 9 successive person-to-person infections [12]. The clinical presentation of typical disease includes fever, characteristic rash, swollen lymph nodes, and, occasionally, varied medical complications [15], similar to those of smallpox, a related Orthopoxvirus infection eradicated globally in the early 1980s. Fortunately, monkeypox virus infection is less contagious than small pox, causes less severe illness, and, although it can also cause severe illness, it is usually self-limiting [12]. Three clades of the monkeypox virus are recognised; Clade I, which is transmitted by rodents and is estimated to cause more severe disease and higher mortality (causes up to 10% mortality) among humans when compared with other clades, but with little human-to-human spread; clade IIa, which is also zoonotic, but has a low mortality among humans; and clade IIb, which has been spreading globally via human transmission and appears responsible for the 2022 outbreaks [16]. Nevertheless, based on the previous outbreaks, Mpox has an appreciable case fatality ratio of 3% to 6% [12].
Potential therapeutic targets for Mpox: the evidence to date
Published in Expert Opinion on Therapeutic Targets, 2023
Siddappa N Byrareddy, Kalicharan Sharma, Shrikesh Sachdev, Athreya S. Reddy, Arpan Acharya, Kaylee M. Klaustermeier, Christian L Lorson, Kamal Singh
MPX is a zoonotic disease. It is caused by infection with Mpox (formerly known as monkeypox) virus (MPXV). MPXV is transmitted via infected skin, body fluids, and respiratory droplets. Symptoms include Flu-like conditions and rashes1. MPXV is a linear double-stranded DNA virus with a genome length of ~ 200 kb, which encodes ~ 200 proteins [2]. It belongs to the order Chitovirales, the family Poxviridae, and the genus Orthopoxvirus. Other examples of the Orthopoxvirus genus are the cowpox virus (CPXV), buffalopox virus (BPXV), vaccinia viruses (VACV), and the variola virus (VARV). Of these, CPXV and BPXV are of veterinary and agriculture importance, and cause zoonotic disease. VACV has been extensively studied since all smallpox vaccines have been derived from VACV.