What is Mpox?

Mpox (previously called monkeypox) is a virus that has received increasing attention over the past few years. However, this disease has a history spanning back to the 1950s. The virus is thought to have originated in the Democratic Republic of Congo (DRC), where the first human infection was reported in 1970.¹

Mpox is a zoonotic disease, meaning it can spread between animals and humans. Specifically, the virus is transmitted via close physical contact. A human could catch the virus from an animal (through a bite or scratch from a rodent or monkey, for example) or by eating infected meat (bushmeat). The virus can be spread between humans by contact with skin or mucous membranes (present in the mouth, nose, and genitals); breathing in the virus; or contact with household items such as clothing, bed linen, and towels used by an infected person.²

In 2022, there was an outbreak of mpox outside Africa in which the virus spread to other countries, including the USA and the UK. In August 2024, the WHO Director-General asserted that the African mpox endemic was a public health emergency of international concern.³ It is believed that the milder of the two clades (groups with a common ancestor) of the virus, clade II, was responsible for this epidemic.⁴ However, clade I has also been reported outside Africa.⁵ As of 31 August 2024, there have been 326 mpox cases declared in the UK.⁶

Mpox symptoms include a skin rash, fever, headache, swollen lymph nodes, and fatigue (low energy).⁵ Most of the time, the virus causes a mild illness that lasts around 3 weeks. Sometimes, however, severe and fatal cases can occur. These are more likely to happen in children, the elderly, and in cases of pregnancy or a suppressed immune system.⁷

How is mpox usually treated and prevented?

Mpox is typically treated much like other viruses with supportive care, pain control, and isolation.

Vaccines are also available for mpox. These work by exposing someone to a weakened or inactive version of the pathogen (a disease-causing microorganism), allowing their immune system to react and build up a defence against it. The immune system creates a “memory” in the form of antibodies (proteins that recognise the pathogen and act to destroy or neutralise it), that can “remember” the pathogen if the individual encounters it again. Therefore, vaccines are a form of prophylaxis (a preventive measure against disease).

Mpox vaccines are available and encouraged for people most at risk of catching this virus. This includes healthcare workers, sex workers and their clients, and people with multiple sex partners.⁵ Since the mpox virus is related to the smallpox virus, the same vaccine is used for both.⁷ This vaccine is proven to be effective at significantly reducing the risk of mpox infection.⁸

Interestingly the vaccine might be effective if used after a person has been exposed to the virus. This is known as post-exposure vaccination (PEP), as opposed to pre-exposure vaccination (PrEP). This will not guarantee protection from mpox, however, as infection can still occur after PEP.⁹ Therefore, it is far better to get vaccinated before potentially being exposed to the virus if you belong to a group of people deemed at increased risk of catching mpox.

A treatment called Vaccinia Immune Globulin (VIG) consists of antibodies against the vaccinia virus (a virus similar to smallpox that is used in smallpox vaccinations) that have been collected from people who have immunity against the virus. It is used to treat the side effects or complications that might be caused by smallpox vaccination.¹⁰ Whether VIG could be effective as an mpox treatment is uncertain. However, it has been proposed for use in people with weakened immune systems. In people who do receive VIG treatment for mpox, an antiviral drug is usually given alongside it.¹¹

There are three antiviral drugs that could be effective against the mpox virus. These include cidofovir, brincidofovir, and tecovirimat. The latter two are approved by the FDA in the USA for mpox treatment.¹² Each has its own strengths and limitations. For example, cidofovir can only be administered via infusion through a vein and can lead to kidney damage so is unsuitable for people with kidney issues. Although brincidofovir can be taken orally and is not associated with severe kidney toxicity, its use might lead to problems with the liver or the gut. Finally, tecovirimat can be used against cidofovir-resistant virus, but could be linked to nervous system toxicity such as tremors and lethargy.¹³ In addition, tecovirimat has been shown not to reduce the duration of mpox lesions on the skin.¹⁴

Advances in mpox treatments

Medical treatments

Research is underway to find a more effective antiviral treatment for mpox. There are a few drugs being investigated that target various stages of the virus lifecycle. Usually, these are drugs used to treat other diseases that have been repurposed. This is advantageous because it means that they are already approved and available for use in humans.

Nitroxoline, an antibiotic used to treat urinary tract infections, is thought to target the same signalling pathways that the mpox virus uses to replicate itself. This drug is appealing because it can also kill off certain bacteria associated with sexually transmitted diseases (i.e., E. coli and N. gonorrhoeae) which might be caught at the same time as mpox.¹⁵

Other potential drugs include atovaquone and mefloquine (traditionally used in the prevention and treatment of malaria) and molnupiravir (effective against the SARS-CoV-2 virus, which causes COVID-19). These three drugs might be more effective than cidofovir at treating mpox. Specifically, mefloquine prevents the virus from entering human cells, whereas the other two drugs target the virus when it is already within cells. The antiviral effects of molnupiravir might not last very long, as it is fairly short-lived in the body. According to one study, atovaquone was found to be the most effective treatment; it reduced the amount of virus in cells by 92%.¹⁶

Rifampicin and ofloxacin are other potential anti-mpox drugs that work by preventing virus assembly within infected cells. This is a stage in the lifecycle of the virus in which the many small proteins that constitute the virus come together and assemble into its final form.

Vaccines

Since the vaccine currently used to protect against mpox is the smallpox vaccine, efforts are being directed towards creating a vaccine specific for the mpox virus.

One area of research interest is in nanovaccines. These are vaccines composed of tiny nanoparticles that can stimulate a response from the immune system. They have advantages over traditional vaccines in that they might be able to induce a faster and longer-lasting immune response by acting in a more targeted and controlled manner.^17,18

Multiple nanovaccines for mpox have been proposed. These different vaccines contain proteins from the virus that are recognised by the immune system as pathogenic. One nanovaccine containing three different proteins, for example, was reported as potentially being effective as a single dose.¹⁹ Compared to traditional vaccines, which typically require multiple doses to be effective, the administration of a single dose vaccine would save time and money. Another vaccine containing four proteins involved in viral function (i.e., how the virus enters cells and how it assembles into its final form) was able to limit the amount of organ damage caused by the virus. However, it was unclear which specific protein was responsible for this effect.²⁰ It is important to note that these vaccines are still in early stages of research and have not yet been tested in humans.

What are the challenges and future directions for Mpox treatment and prevention?

As with many emerging diseases, finding a safe, effective, and accessible treatment is critical to prevent future outbreaks spreading. 

Now that the mpox endemic in Africa has reached concerning levels, researchers on the continent will need financial support to tackle this virus effectively.²¹ Progress is being made, with the first 100,000 mpox vaccine doses being delivered to the DRC on 5 September 2024,²² but more must be done.

Smallpox was eradicated in 1980. However, there are concerns that mpox could potentially replace this virus. Due to the completion of smallpox vaccination programmes many years ago, the majority of people younger than 40 years are unvaccinated and thus unprotected from the virus. Hence, an effective vaccine specific for mpox is crucial, as this will prevent the spread of mpox in susceptible and vulnerable populations.

Summary

• Mpox originated in the Democratic Republic of Congo over 50 years ago. However, the virus spread beyond the African continent in 2022, causing the most recent epidemic
• Typically, treatment for the disease consists of supportive care, pain medication, and isolation to prevent spread. Some antivirals are also approved for mpox treatment
• The smallpox vaccine is being used to prevent mpox infection; vaccination is recommended in high-risk populations
• Drugs used in different diseases are being researched and repurposed to treat mpox. These target various stages in the lifecycle of the mpox virus
• Nanovaccines have the potential to prevent mpox and have some advantages over traditional vaccines; however, these are currently under research