Treating Monkeypox: Current Medical Approaches

Overview                                  

Monkeypox is an emerging disease that can be transmitted from animals to humans. It comes from a virus called orthopoxvirus in the Poxviradea family. Cases of monkeypox in humans are seen in areas where smallpox has been eradicated. Monkeypox virus tends to spread among mammals, including humans.¹

The illness is originally from the Democratic Republic of Congo, where the first case was reported in 1970. Nonetheless, many cases of monkeypox have been reported in humans and wildlife in Central and West Africa. In recent years, there has been a notable rise in the occurrences of human monkeypox virus, accompanied by an expansion of its geographical reach. This is linked to a decline in immunity resulting from smallpox vaccination.¹

In 2017, Nigeria confronted the largest flare-up of monkeypox virus in the West African clade. Two cases of monkeypox were brought into the United Kingdom through Nigerian persons in September 2018, and one became the source of hospital-acquired infections affecting healthcare workers. Moreover, the monkeypox virus was imported to the United States of America in 2003 through rodents that were transported from Ghana and cohabitated with prairie dogs. These prairie dogs subsequently became the source of infection in humans.¹

Monkeypox is a condition that resolves on its own, and its symptoms typically persist for a duration of two to four weeks. The early signs and symptoms are usually non-specific including headache, malaise, backache, fatigue, lethargy, and low-grade fever. Then twelve to sixteen days after exposure, a vesiculopustular rash begins on the face and trunk and then spreads to other body parts. The pustules later form crusts that subsequently peel off after one to two weeks. Initial signs and symptoms of monkeypox infection are identical to smallpox; however, unlike smallpox, lymphadenopathy is a distinguished feature. Clinical outcomes are generally worse in patients with weakened immune systems, extended exposure to viral particles and the occurrence of complications such as bronchopneumonia, encephalitis, and visual loss due to corneal infection.²

Monkeypox can be suspected in an individual with the symptoms mentioned above, particularly if there is a history of contact or travel to areas where monkeypox is commonly found. A suspected case of monkeypox can be confirmed using the polymerase chain reaction test.²

It is believed that the virus is spread through respiratory secretions and saliva, or direct contact with the fluid or crust material of the infected area. There's also a possibility of the virus being passed through poop.¹

Although lacking a significant tendency to transmit among humans, the monkeypox virus constitutes a serious danger to life in the region of the Democratic Republic of Congo, West and Central Africa, and possibly globally. In 1980, the World Health Organization recognised the monkeypox virus as the most important orthopoxvirus infection in humans after the elimination of smallpox; thus, monitoring is warranted. There is no current evidence showing that human-to-human transmission can sustain the monkeypox virus in local communities. However, a study proposes that frequent exposure to animals infected with monkeypox in a population with low herd immunity can lead to large groups of people infected with monkeypox virus in the African rainforest. Like smallpox, the monkeypox virus could be a danger in biological warfare; hence, several antivirals and therapeutic medications are being developed.¹

This article aims to delve into the current treatment strategies for monkeypox. Stay tuned for further information!

Supportive care and symptom management

At the moment, there are no definite treatments approved for monkeypox. Luckily, the clinical course of monkeypox infection is usually mild and resolves on its own. Therefore, it rarely requires specific therapy, and treatment is often supportive. Supportive therapy may include medications that reduce fever, painkillers, or antibiotics for secondary bacterial infections. However, certain patients may warrant specific treatment such as those with severe disease, patients with weakened immune systems, pregnant women, and the paediatric age group.²

Antivirals

Various antivirals may be efficacious in treating monkeypox infections, although these medications were approved for the management of smallpox based on animal models. Dose studies for these medications have been conducted in humans, yet their effectiveness has not been fully determined. Hence, medications for monkeypox infection are still under research. To date, only five medications have been considered for treatment: tecovirimat, brincidofovir, cidofovir, trifluridine, and vaccinia immune globulin (VIG).³

Tecovirimat 

Tecovirimat (also known as TPOXX or ST-246) is the first antiviral indicated for the treatment of smallpox in adults and paediatric patients weighing at least 3 kg and is deemed the treatment of choice. In patients with severe disease, combination treatment with tecovirimat and brincidofovir may be used.⁴

While the efficacy of tecovirimat in humans against monkeypox has not been tested, studies have reported improved survival from fatal monkeypox virus infections in animals treated with tecovirimat compared to animals given a placebo at different stages of the disease. In a bigger safety study with 359 people taking tecovirimat, the side effects from the placebo were mostly the same as those from tecovirimat.⁴

The CDC-held Emergency Access Investigational New Protocol permits the use of tecovirimat for non-variola orthopoxvirus infections such as monkeypox. The protocol also encompasses allowance for opening an oral capsule and blending its content with liquid or soft food for children weighing less than 13 kg. Tecovirimat is available through the Strategic National Stockpile as an oral capsule formulation or an intravenous vial.⁴

Brincidofovir and Cidofovir 

Brincidofovir has been approved for the treatment of smallpox in the US since June 2021. Brincidofovir, taken orally, is an analogue of the intravenous medication cidofovir. It is believed to offer a potentially safer option with reduced risk of kidney toxicity compared to cidofovir.⁴

While studies evaluating the use of brincidofovir for treating monkeypox infections in animal models are scant, brincidofovir has been shown to be efficacious against orthopoxvirus infections. Clinical data regarding the effectiveness of cidofovir against monkeypox in humans is insufficient. However, it demonstrated activity outside the living organism and efficacy against fatal monkeypox virus infections in animals.⁴

Intravenous normal saline and probenecid therapy must be given simultaneously with cidofovir. For brincidofovir, liver function tests must be performed before and during treatment, as brincidofovir may cause increases in serum transaminases and serum bilirubin. These therapies are available under an Emergency Use Authorization or Investigational New Drug application.⁴

Vaccinia Immune Globulin (VIG)

VIG is a hyperimmune globulin licensed by the FDA for the treatment of certain complications of vaccinia vaccination. Although there's a potential for VIG to be a treatment for monkeypox and smallpox, there is a significant lack of data regarding its effectiveness. Furthermore, the use of VIG for either monkeypox or smallpox has not undergone testing in humans. Since vaccination with the vaccinia virus vaccine is avoided in patients with severe immunodeficiency in T-cell function, such patients with exposure history may alternatively be given VIG. Treatment with VIG should be carried out under an Investigational New Drug application.⁴

Trifluridine

Limited data exists on the management of ocular (eye) manifestations specifically related to monkeypox disease using trifluridine. Trifluridine eye drops, typically prescribed for conditions such as herpes simplex keratitis and vaccinia, have been approved for use in this context.

Administered as a 1% ophthalmic solution, the usual protocol involves applying a single drop every 2 hours until re-epithelialization is achieved, after which the frequency is reduced to every 4 hours. Prolonged use beyond 3 weeks is avoided due to potential toxicity concerns, although trifluridine is generally well-tolerated. Common adverse effects include a transient burning sensation and eyelid oedema.³

Concluding remarks

• Monkeypox is an emerging disease caused by the orthopoxvirus, with a significant transmission potential from animals to humans, particularly in areas where smallpox has been eradicated.
• The Democratic Republic of Congo and regions of Central and West Africa have witnessed an increase in human monkeypox cases, possibly due to declining immunity post-smallpox vaccination.
• Although primarily observed in Africa, cases of monkeypox have been reported in other regions due to travel-related transmission, as seen in instances in the United Kingdom and the United States.
• Clinical manifestations of monkeypox are similar to smallpox initially, but with distinguishing features such as lymphadenopathy.
• Despite limited human-to-human transmission, monkeypox remains a significant concern, particularly in regions with low herd immunity and frequent exposure to infected animals.
• There are no specific treatments approved for monkeypox, with supportive therapy being the mainstay. However, certain patient groups may require targeted interventions.
• Several antivirals, including tecovirimat and brincidofovir, show promise in treating monkeypox, although their efficacy in humans is still under investigation.
• Other potential treatments include vaccinia immune globulin (VIG) and trifluridine, with limited data available on their effectiveness in managing monkeypox.