Mpox, previously known as monkeypox, is a rare zoonosis caused by an orthopoxvirus and in general, produces a mild flu-like illness and rash in humans. Virologically and clinically the condition is similar to smallpox, the first and only viral disease to be eradicated by humans. In 2022, a new outbreak of mpox was identified in the UK, with spread mostly to Europe and the Americas.
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Epidemiology
Since the diagnosis of the first human case of mpox in August 1970 in the Democratic Republic of the Congo, the disease has become endemic in several mainly Central and West African states. In 2003, an outbreak of 72 cases in the United States, transmitted by pet prairie dogs, were the first reported cases outside Africa, but no human-human transmission occurred in this outbreak 1,8.
In 2022, a new outbreak of cases, all infections of the West African clade, first in the United Kingdom and then elsewhere in Europe and the US, occurred. This is the first time that any chains of transmission have been demonstrated in Europe without evidence of an epidemiological connection to known endemic areas in Africa 2.
The majority of cases have been found in men, and it seems to be more common in adults now, although historically (the 1970s-1990s) was more common in children 1. Fortunately, mortality rates are low, with almost all children under the age of 10 years 6,7. There have been 12 deaths amongst >35,000 cases as of September 2022 14.
It is interesting to consider why mpox appears to be on the rise in the 2000s; prevailing wisdom suggests that it is the combination of two main factors, firstly the decline of population-wide immunity against smallpox. Secondly, the continual encroachment of humans into previously wild areas following environmental degradation 3.
Clinical presentation
In most mpox cases, the presentation starts with a typical febrile prodrome:
chills
headache
exhaustion
myalgia and/or arthralgia
backache
lymphadenopathy
Novel features of current outbreak 16:
penile edema
anorectal pain
impotence
Rash
A classic rash develops a few days after the prodrome. Initially, macules appear, which evolve to papules, then vesicles, and finally pustules, which then crust over. By four weeks the scabs fall off. Each stage of the rash lasts 1-2 days. These lesions develop in a synchronous fashion, i.e. all the lesions change in lockstep.
Rash distribution is usually centrifugal, i.e. it predominates on the face and extremities, with relative sparing of the torso (cf. centripetal rash of VZV). In the 2022 outbreak, many patients have had genital rashes 2,12.
The World Health Organization (WHO) reports involvement of the oral mucous membranes in 70% of cases, and conjunctival involvement in 20% of cases, with corneal involvement also possible 12.
A large study of 528 patients from 16 countries published in 2022 demonstrated that 95% cases present with a skin rash, 73% with anogenital lesions and just over 40% with mucosal disease 15. A similar but smaller study of 197 patients attending a single large London hospital found that penile edema and anorectal pain were novel features of the current mpox outbreak 16.
Complications
Encephalitis
Rarely mpox cases may develop encephalitis, and this has been seen both in Africa and in the United States; in some cases, it is fatal 4,6,8,9.
HIV coinfection
A concurrent HIV infection seems to lead to more severe disease than in HIV-negative mpox cases, in particular 4:
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skin
larger lesions
more likely genital involvement
longer disease course
more superadded bacterial infections
Deep tissue abscess formation
Some observational studies report the formation of deep tissue abscesses, which are not necessarily adjacent to superficial mucocutaneous lesions 11. At least one case of retropharyngeal abscess has been reported, causing tracheal airway compromise 13. It is unclear if abscess formation requires superimposed bacterial infection.
Ophthalmological complications
A significant proportion of mpox cases develop ophthalmological symptoms related to the disease, including conjunctivitis and corneal scarring secondary to corneal lesions 10.
Pathology
Etiology
Mpox virus (MPXV) is a member of the Orthopoxvirus genus, from the Poxviridae family. Smallpox virus (variola virus) is a close relative. Genetically, there are two clear-cut clades of mpox, Clade I (previously known as Central African (or Congo Basin) clade) and Clade II (previously known as West African clade). The current outbreak is officially caused by the subvariant clade IIb according to the WHO 14. The virus is a double-stranded DNA virus with a protein envelope 1,5,7.
Transmission
It is primarily a direct zoonosis i.e. most cases are from direct contact with animals, person-to-person transmission is rare.
airborne droplets
close contact
eating bushmeat
Although the current outbreak in the UK was clustered in men having sex with men, it is not thought to be a sexually-transmitted infection, and rather is due to close human contact and associated transmission 2.
Radiographic features
CT
Lymphadenopathy can be a prominent feature detected on CT, albeit non-specific. In some cases, cutaneous lesions may also be visible on CT.
MRI
The appearance of mpox encephalitis has been reported on MRI of the brain, the reported features - in a single case in a 6 year old girl - were diffuse edema, increased FLAIR signal in the thalamus and parietal cortex and meningeal enhancement 8.
Treatment and prognosis
Supportive care is the only treatment currently advised for mpox. Some experimental antivirals have shown activity in animals and have been tried with some success in sicker cases 2.
Fortunately, the existing vaccine against smallpox has been found to be up to 85% effective against mpox in retrospective data analyzes 1.
Fortunately, in most cases, mpox is not serious, and no deaths have ever been reported outside Africa. In a large series of 282 cases published in 1987, the only deaths were reported in children under 10 years old 7.
History and etymology
Mpox was first isolated in 1958 in macaque monkeys in a Danish laboratory. However, mpox is a misnomer as the main hosts in the wild are thought to be rodents. The first documented human patient was a 9-month old infant in the Democratic Republic of the Congo in August 1970, which was called Zaire at the time 1,7.
In 2003, there was an outbreak of 72 cases, 34 confirmed, and a further 38 probable, in the United States which were transmitted by pet prairie dogs which acted as the vector; these were the first reported cases outside Africa. The origin of the outbreak was sourced to a batch of imported infected rodents from Ghana which entered the US in April 2003. These small mammals included Gambian giant pouched rats, rope squirrels, and dormice 1,8.
The pouched rats were transported with prairie dogs as they traveled to an animal distribution center in Illinois; during transit, the prairie dogs caught the mpox from the giant pouched rats. From Illinois, the prairie dogs were passaged to a further distributor in Wisconsin, and then onto pet stores where consumers purchased the infected animals 1,8.
On 24 July 2022 the World Health Organization (WHO) deemed mpox a public health emergency of international concern. On 4 August 2022 the United States followed suit with a similar declaration 14.
The WHO changed the name of the virus from monkeypox to mpox in November 2022. This followed the use of stigmatising language by people and the media. It has similarly amended the names of the main clades of mpox. This is consistent with WHO recommendations that the names of diseases do not refer to a specific place or animal to decrease the risk of stigma 18. Similarly, the WHO used Greek letters instead of place names to refer to new variants of COVID-19 18.
The WHO is working to establish mpox as the accepted name of the condition, and mpox will be included in the International Classification of Diseases (ICD). The intention is to use both mpox and monkeypox for one year, gradually phasing out the older term 17,18.
Differential diagnosis
The main clinical differential diagnoses are other orthopoxviruses as well as common causes of vesiculopustular rashes:
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varicella zoster virus (VZV)
centripetal rash: a centrifugal rash is very rare in chickenpox
lymphadenopathy is unusual in chickenpox
herpes simplex virus (HSV)
secondary syphilis