Author: Patrick Toh
Editor: Altay Shaw

Reports of the 2022  monkeypox (Mpox) outbreak have flooded the news, spreading from their endemic regions into countries that were unaffected before, like Kenya, Burundi, etc. Small cases have been reported in countries outside of Africa like the US, the UK, and Pakistan. Recently, the World Health Organisation (WHO) also declared monkeypox a global health emergency, with some suggesting it could be the ‘next’ COVID-19 outbreak. Cases have also been reported in the US, UK, and Pakistan. Despite the news, many laypeople do not fully understand what monkeypox is. With the help of a review article done in 2023, I can summarise Monkeypox’s history, transmission, pathogenesis and treatment.

History of Monkeypox

The first discovery of Monkeypox was in 1958 when a shipment of monkeys from  Singapore to Denmark were transported. Later in the decade, the US, the Netherlands, and France reported more cases of monkeypox in captive monkeys The first human monkeypox case was reported in a 9-month-old boy in 1970 from the Democratic Republic of Congo. Following this, children in rural, rainforest areas in West and Central African countries reported further sporadic outbreaks of cases. Originally, the type of Mpox virus reported during 1981–2017 was usually caused by the clade 1 virus, but on May 13th 2022, a global outbreak reported a new type of monkeypox virus called clade IIb, which not only affected their endemic regions in Africa but had reported cases in unaffected countries before the outbreak.

What is monkeypox?

Virology of Monkeypox

Monkeypox is an orthopoxvirus, which is a double-stranded DNA virus that shares the same genus with various viruses like the variola virus, vaccinia virus, and cowpox virus. They have a brick-like shape and range from 200 nm to 250 nm, which is similar in shape to the variola and vaccinia viruses’ virions. Its genome is about 200 kilobase pairs and encodes roughly 190 proteins worth of viral particles and other proteins that modulate the numerous host processes. There are two types of the monkeypox virus; clade 1 is responsible for causing monkeypox in Central Africa and the Congo basin, whereas clade 2 monkeypox is found in West Africa. As of the 2022 outbreak, the new B.1 lineage is classified as clade 2b and has been identified as the new variant of clade 2 Mpox. The main feature of monkeypox is that its double-stranded DNA is stable, and DNA polymerase has proofreading exonuclease activity, which means they have a low mutation rate and result in lower transmission.

Transmission of monkeypox

There are multiple ways in which monkeypox can be transmitted. Animal-to-human transmission is one of them, they can be from a non-invasive exposure to infected animals, like exposure to a dead infected animal. Infected animals can also bite or scratch individuals to transmit the virus, with the former being a lower risk of transmission. Human-to-human transmission of monkeypox can occur in several ways, like the secretion of respiratory droplets, direct contact, vertical transmission from pregnant women to foetuses, percutaneous transmission, or contact with infectious particles via objects like bedding. The most common way monkeypox can be transmitted is through sexual contact like the contact of bodily fluids. 

Epidemiology

Moreover, it was found during the 2022 outbreak that homosexual men were more likely to be infected with the Monkeypox virus compared to heterosexual men, likely due to sexual contact being a risk for monkeypox. Furthermore, children, pregnant women and immunocompromised patients were more likely higher risk groups to be infected with monkeypox.

Treatment

Treatment normally includes general supportive care and the use of antivirals for immunocompromised patients. Examples of supportive care include giving fluids to dehydrated patients, draining and wound management of rashes. Additionally, smallpox vaccination has been shown to provide 85% protection against monkeypox, so researchers have recommended giving smallpox vaccines to those affected by Monkeypox or to those at high risk in regions affected by monkeypox.

Pathogenesis of Monkeypox

The clinical symptoms of the monkeypox virus are highly dependent on the transmission route, dose and strain of the infecting virus. For example, when the monkeypox virus infects the respiratory tract, it infects epithelial cells in the airway, whereas viruses which affect the skin infect keratinocytes, fibroblasts, and endothelial cells, common types of cells within the skin. Monkeypox viruses can also infect immune cells, specifically the antigen-presenting cells, their role is to carry antigens to lymph nodes, and so this feature allows Mpox to survive long enough to infect other immune cells or cells. How the monkeypox virus replicates is similar to all other viruses, in that gene expression, viral replication, and virion assembly within the host cell’s cytoplasm create a mature virion with a single lipid membrane. Finally, when released an additional envelope is added to the virion.

The infective stage described above is called the first viraemia stage. The second viraemia stage is when the virus can spread to the lymph node and other major organs like the liver. This stimulates the humoral and cellular immune response, releasing antibodies to induce long-term immunity in affected individuals. 

The viraemic phase of monkeypox is usually a stage where the main clinical feature of rashes isn’t present, they usually last 1–5 days, but other symptoms include fever, myalgias, sore throat, and an enlarged lymph node. When skin rashes do erupt, they last for 2-3 weeks and progress through several stages from macules into papules, vesicles, and then pustules. Before the 2022 outbreak, monkeypox rashes would be located across the entire part of the body, but after the 2022 outbreak, researchers discovered that rashes were mainly located on the anogenital and perioral areas, the lower third of the face.

Summary

Now, the main question is whether the monkeypox outbreak can be as serious as the recent COVID-19 pandemic. First of all, it’s important to note that, unlike COVID-19, monkeypox is less likely to mutate due to its’ extremely stable DNA.  Additionally, there are interventions available both pre- and post-exposure for monkeypox, though these treatments have not been formally licensed. We should be cautious and ensure funding is available to treat monkeypox.