Monkeypox: What Is It, and How Can We Prevent It?

Health Letter, December 2022

By Nina Zeldes, Ph.D.

On July 23, 2022, the World Health Organization declared monkeypox a “public health emergency of international concern.” This outbreak is unusual: Not only is it the largest outbreak of this disease so far — as of Nov. 25, more than 80,000 cases of monkeypox have been reported globally — but most cases have been reported outside of Central and West Africa, where this virus usually is found. In fact, with over 29,000 cases, the U.S. has the largest number of infections during the current outbreak, which so far have led to 14 deaths.

What is monkeypox?

Monkeypox is a disease caused by the monkeypox virus. This virus belongs to the orthopoxvirus family, which also includes smallpox, a severe disease that has been eradicated worldwide since 1980. The monkeypox virus was first described in 1958 when monkeys in a research facility became sick. However, despite its name, its origin and host animals remain unknown.

There are two main types of monkeypox virus. The current outbreak is caused by a type called Clade IIb, which is milder than the other type, Clade I, which is more likely to cause death.

According to the Centers for Disease Control and Prevention (CDC), the symptoms of monkeypox tend to start about three weeks after exposure and can begin with one to four days of flu-like symptoms, such as fever, fatigue, swollen lymph nodes, muscle aches and headaches. In the early stages of the second phase, patients develop one or several skin lesions that often look like blisters or pimples. These lesions form on or near the genitals; anus; hands; feet; face; or on the soft tissue (mucosa) inside the mouth, genital or anal areas.

These lesions can cause severe pain, especially when they get infected, and can become itchy when they heal. In the current outbreak, about 10% of patients need to be hospitalized, often to help treat their extreme pain.

To avoid infecting others, patients should follow CDC guidance and isolate as soon as their symptoms start until their rash has healed and a new layer of skin has formed at the site of their lesions.

In the current outbreak, the virus has spread mainly through direct and prolonged contact with monkeypox lesions (for example, during sex). The virus also can spread in other ways, such as though bedding or clothing that has been in contact with bodily fluids of infected patients, in particular with the fluids from inside the skin and mucosal lesions. However, early studies show that without direct skin-to-skin contact, the risk of infection seems to be relatively low. For example, very few health care workers have gotten infected themselves after treating patients with confirmed cases of monkeypox, even if they did not wear the recommended personal protective equipment, such as gloves, masks and eye protection, and were not vaccinated after their exposure as a precaution.

Treatments

There are currently no treatments available for monkeypox that have been approved by the Food and Drug Administration (FDA). Instead, most patients have to manage their symptoms with pain medications such as ibuprofen (ADVIL, MOTRIN) or acetaminophen (TYLENOL).

Even without treatment, most patients recover from a monkeypox infection within two to four weeks. However, some experience complications, including secondary infections and scarring, which can lead to blindness if the lesions formed in the eye.

Because monkeypox belongs to the same family of viruses as smallpox, drugs that were originally developed for that disease are currently also being used to treat patients with severe monkeypox infections.

One of these drugs is the antiviral tecovirimat (TPOXX). It was approved by the FDA in 2018 to treat smallpox. A trial with healthy human volunteers (who did not have smallpox or monkeypox at the time) showed that the safety risks of this drug are acceptable. Common adverse effects include headache, nausea, vomiting and stomachache.

But because of the potential dangers of studying smallpox in animals, tecovirimat was approved based only on efficacy data from animals infected with other orthopoxviruses (monkeypox virus in nonhuman primates and rabbitpox virus in rabbits). Importantly, there is also no clinical trial data available yet on how effective tecovirimat is for the treatment of people infected monkeypox or which patient groups will benefit the most.

For this reason, this drug is considered an investigational or experimental drug. If physicians want to prescribe it to their patients, they will need to request special permission from the CDC.

Widespread use of this drug is not recommended, mainly because the CDC is concerned that the monkeypox virus could become resistant to tecovirimat. This could mean that the only potential treatment for monkeypox someday would no longer be effective for severely sick patients. The CDC therefore recommends the use of tecovirimat only for two groups of patients: those who are severely ill, including patients whose lesions develop bacterial infections that lead to sepsis and patients whose lesions are in areas where scarring could cause long-term complications.

Use of tecovirimat also should be considered for patients who have a high risk of becoming severely sick. This group includes patients with weakened immune systems, certain cancer patients, organ transplant recipients or patients with autoimmune diseases or HIV; patients with certain skin conditions such as eczema; and young children or patients who are pregnant or breast-feeding.

Vaccines

The FDA has approved only one vaccine, called JYNNEOS, for the prevention of monkeypox in adults at high risk for the disease. Jynneos, which also is approved for prevention of smallpox, contains a live, weakened version of another type of orthopoxvirus that is unable to replicate (reproduce) and is given in two injected doses 28 days apart. People are considered vaccinated two weeks after the second dose.

Another vaccine called ACAM2000, which is approved by the FDA only for preventing smallpox, may be used for the prevention of monkeypox on an experimental basis under the agency’s Expanded Access Investigational New Drug program. It contains a live, weakened version of the Vaccinia virus, which is another type of orthopoxvirus. ACAM2000 is given as a single dose via multiple punctures in the skin, and people are considered vaccinated 28 days after the vaccination. The ACAM2000 vaccine generally is not tolerated as well the Jynneos vaccine.

However, vaccination against monkeypox is not recommended for everyone. According to the CDC, only those who have already been exposed, have been in close contact with someone who was diagnosed with monkeypox or have a higher risk of getting infected should get vaccinated.

Although little is known about how effective the vaccines are for the prevention of monkeypox or how long the protection lasts, there are indications that they work. For example, a CDC report showed that people who were not vaccinated were 14 times more likely to get infected than those who received the vaccine.

Although over one million doses of the Jynneos vaccine have been administered in the U.S. as of October 2022, vaccine availability is limited. To stretch the supply, different vaccine strategies have been used. Instead of the required two doses, many have only received a single dose or even a much lower dose administered intradermally (into the skin).

These adjusted vaccine strategies may not provide enough protection from monkeypox, and even with the full dose, these vaccines do not provide “instant protection.For example, several patients got sick before they were fully vaccinated and in some cases breakthrough infections were reported in patients who were fully vaccinated.

What will happen next?

During the current monkeypox outbreak, the majority of cases in the U.S. have been concentrated amongst gay, bisexual and other men who have sex with men.

The number of daily reported infections in the U.S. has fallen significantly since August. This drop in cases is most likely due to a combination of factors, such as the rollout of the vaccinations as well as changes in behavior and increased immunity in the groups most at risk. Despite this, the CDC warns that monkeypox may not be eradicated in the U.S. but may continue to spread, albeit at a very low level.

Additionally, not all countries have seen a reduction in monkeypox cases. For example, the number of infections is rising in Nigeria, where vaccines remain unavailable. It is also important to remember that sporadic outbreaks of this disease, including infections due to the more deadly type, Clade I, have been reported in West and Central Africa for years, often affecting women and children.

Concerningly, not everyone who needs vaccines or treatment for monkeypox can access them. For instance, within the U.S., many of the communities most at risk remain underserved: although more than 30% of monkeypox patients are Black, only about 11% have received at least one dose of the vaccine.

Additionally, although the U.S. has the largest number of monkeypox cases, these cases amount to only 36% of worldwide infections. Yet the U.S. holds 80% of the global monkeypox vaccine supply. Not only is the global supply limited, but the current estimated price of $110 for one dose of the monkeypox vaccine is also prohibitive for many countries. However, a new report has identified nine additional manufacturers that would be capable of producing monkeypox vaccine at a fraction of the current price. Ramping up vaccine production would be an important step to increase accessibility of doses for those in need.

As we have seen with this and other outbreaks, infectious diseases that start in one region or community can easily spread much more broadly. The current monkeypox outbreak is just one of many examples, such as COVID-19 and HIV, that have clearly demonstrated that equitable access to vaccines and treatments are of utmost importance to protect everyone, especially those most at risk, from similar outbreaks in the future. It is well past time for us to learn this lesson.