MPox (formerly Monkeypox)

Introduction

MPox (previously known as monkeypox) is a rare zoonotic disease caused by the monkeypox virus (MPV), which belongs to the genus Orthopoxvirus, along with variola virus, the causative agent of smallpox.^1,2

MPV has emerged as the most important Orthopoxvirus for public health and has caused an ongoing outbreak in the UK, beginning in May 2022.³

This article presents a clinical summary of MPV, including its epidemiology, clinical features, and management.

Epidemiology

MPV is endemic to the Democratic Republic of Congo, where the virus was first isolated in 1970.²

There are two clades of the virus: the Central African (Congo Basin) clade, and the West African clade.¹ The former is more prone to cause severe disease, with a case-fatality ratio (CFR) of up to 11%, whereas the latter has a CFR of <1%. 

Since the eradication of smallpox in 1980, MPV has emerged as the most important Orthopoxvirus for public health, and incidence may be exacerbated by waning immunity following the cessation of smallpox vaccination, which conferred 85% protection to MPV.²

Prior to 2003, outbreaks of MPV were limited to Africa, with cases reported in 10 countries. The first outbreak outside of Africa occurred in 2003 when a shipment of wild rodents from Ghana is thought to have infected pet prairie dogs in the USA.²

Over the following years, cases were reported in Israel, the UK, and Singapore.⁴

Aetiology

The monkeypox virus (MPV) is a double-stranded DNA virus belonging to the genus Orthopoxvirus. This group contains four other virus species pathogenic to humans, including cowpox virus, vaccinia virus, and variola virus, the causative agent of smallpox.^1,2

Pathophysiology⁸

MPV, and other species of Orthopoxvirus, bind to the cell surface through interaction between their ligands and several different cell surface receptors, before gaining entry via fusion or endosomal uptake.

Replication occurs in the cytoplasm of cells at the site of infection, where pre-made viral proteins stimulate the expression of early genes which promote DNA replication, as well as transcription and translation of intermediate and late genes, which code for structural proteins. Thus, nascent virions are assembled and spread to lymph nodes.

MPV has an incubation period of 7-17 days before the onset of symptoms.

Transmission⁹

Transmission occurs when the virus gains access through broken skin, the respiratory tract or the mucous membranes. MPV is zoonotic, and although the host reservoir is still unknown, species of African rodents are implicated.

Animal-human transmission occurs through direct contact with blood, bodily fluids, or cutaneous or mucosal lesions of infected animals.

Human-human transmission is rarer and occurs through saliva and respiratory excretions, direct and indirect contact with lesion exudate or crust material or vertical transmission via the placenta, or close contact during or after birth.

Risk factors

Individuals who have travelled to endemic countries and been in contact with infected individuals or animals are at increased risk of acquisition.

Immunocompromised individuals, such as children and pregnant women often have more severe disease, along with those with underlying immune deficiencies.

People younger than 40-50 may be more susceptible due to the cessation of smallpox vaccination.⁷

Clinical features

The disease is often self-limiting, with symptoms usually resolving within 2-4 weeks. The clinical features associated with MPox infection mirror that of smallpox.

The prodromal phase lasts between 1-4 days and includes fever, headaches and fatigue.^1,2

Importantly, a distinctive feature of MPV infection is maxillary, cervical or inguinal lymphadenopathy (maxillary, cervical or inguinal), which is absent in similar diseases such as chickenpox, measles, and smallpox.⁷

Around 1-3 days following the prodromal phase, a distinctive rash appears, with the number of lesions varying significantly.^1,2 This characteristically appears on the face before taking a centrifugal distribution¹, with the following body parts affected: ⁹

• Face (95%)
• Palms of hand and soles of feet (75%)
• Genitalia (30%)
• Conjunctiva/cornea (20%)

The lesions, shown in Figure 1, develop sequentially from macules to papules and to vesicles (1A) containing clear fluid.¹⁰

Vesicles then become well-circumscribed, umbilicated pustules (1B, 1C) before ulcerating (1D) and crusting over (1E, 1F). The infection can last up to 4 weeks until the lesions desquamate.^1.2

Differential diagnoses

The WHO recommends suspecting MPox in any person in a non-endemic country with an unexplained acute rash accompanying either headache, acute onset fever, lymphadenopathy, myalgia, back pain or asthenia if the rash cannot be explained by more common causes, such as chickenpox, shingles and herpes simplex. ⁴

Table 1. Differential diagnoses for MPox.^1,2,11

Diagnosis

Diagnosis of MPV relies on the detection of viral DNA using PCR testing.⁴

Samples should be obtained from swabbing the roof, fluid, or crust of skin lesions. Antigen detection and antibody serology testing are not recommended for the diagnosis of MPV due to their cross-reactivity with other orthopoxviruses.

Management

In the first instance, patients with suspected MPox should be isolated, and given supportive care.

Antivirals may be used such as cidofovir, a DNA polymerase-inhibitor, and tecovirimat, which inhibits the viral envelope protein.¹¹

Prevention

WHO recommends reporting illnesses associated with travel to endemic countries, avoiding contact with infected animals and avoiding eating or handling bushmeat, as well as using hand hygiene and alcohol-based sanitiser.⁴

Prompt contact tracing and surveillance protocols should be employed to curb onward transmission. Health workers should observe contact and droplet infection control precautions. ¹²

Although prior smallpox vaccination confers 85% protection against MPox, populations under the age of 50 may no longer benefit due to its cessation following the eradication of smallpox.

The UK Health Security Agency (UKHSA) is offering the smallpox vaccine Imvanex to high-risk contacts of patients diagnosed with MPox to reduce symptomatic infection and severe illness. ³

Complications

Severe complications are more common among unvaccinated (74%) than vaccinated (39.5%) patients; bacterial skin infections were noted in 19% of unvaccinated MPox patients, and other complications may include bronchopneumonia, vomiting, diarrhoea, and dehydration.^1,2

Other complications include ocular infections, loss of vision and sepsis in severe cases. Congenital MPV and stillbirth can occur in pregnant women.

Key points

• MPox is a rare zoonotic disease caused by the monkeypox virus (MPV)
• MPV has caused an ongoing outbreak in the UK, however, a WHO risk assessment has stated that the risk of potential onward spread in the UK is minimal
• MPV is transmitted from animals to humans through direct contact with blood, bodily fluids, or cutaneous or mucosal lesions of infected animals.
• Human-to-human transmission is rarer and occurs through saliva/respiratory excretions, contact with lesion exudate or crust material or vertical transmission via the placenta, or close contact during or after birth
• Risk factors include travel to endemic countries, contact with infected individuals or animals, and immunocompromised states
• The disease is often self-limiting. Symptoms include fever, headaches, and fatigue before the appearance of a rash
• Lesions appear most commonly appear on the face and peripheral body parts and develop sequentially into vesicles and pustules which ulcerate and crust over
• Diagnosis requires lesion swabs and PCR testing
• Management is largely supportive, but antivirals such as cidofovir and tecovirimat may be used, and smallpox vaccines may be offered to high-risk contacts
• Common complications include bacterial skin infections, bronchopneumonia, vomiting, diarrhoea, and dehydration.

Editor

Dr Chris Jefferies

References

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12. UK Health Security Agency. GOV.UK. 2022. Monkeypox: background information. [Accessed 25 May 2022] Available from: [LINK]