Mpox (formerly known as monkeypox), a disease caused by infection with the monkeypox virus, is suddenly in the news. The virus, which can cause flu-like symptoms, a painful rash and swollen lymph nodes, is related to other poxviruses that can infect humans and animals, including those that cause smallpox and cowpox.

Historically, virtually all cases of mpox—outside of a few limited outbreaks—have occurred in Central and West Africa, where it has been a rare, endemic disease. But in May 2022, cases of mpox began to be reported in Europe and the United States.

What began with just a handful of cases a few months earlier had ballooned to over 80,000 cases globally by late November, with over 29,000 cases in the U.S.. On August 4, 2022, the Biden administration declared mpox a public health emergency and took steps to ease access to vaccines.

“Monkeypox is a viral infection for which prevention and treatment options are available,” says Yale Medicine infectious diseases specialist Marwan Azar, MD. “A smallpox vaccine, Jynneos, is effective in the prevention of monkeypox in patients without exposure. In persons exposed to another individual with monkeypox, Jynneos may prevent the development of the disease if given within a few days of the exposure.”

Treatments for smallpox can accelerate the resolution of mpox, he adds. “In particular, tecovirimat, an antiviral that targets the envelope protein of the monkeypox virus, may shorten the duration of illness, reduce the risk of death, and is generally very well tolerated,” says Dr. Azar. “Even without treatment, the mortality rate of monkeypox during the 2022 outbreak is very low, at less than 0.03%”

The monkeypox virus is an orthopoxvirus, a group of closely related viruses that includes the virus that causes smallpox. It was discovered by researchers in Denmark in 1958, when two outbreaks occurred in laboratory research monkeys that developed a pox-like rash. Because it was first identified in monkeys, the researchers called it the monkeypox virus. In November 2022, the World Health Organization (WHO) changed the name of the disease to mpox with the aim of reducing the stigma that has been linked to the term “monkeypox.” The virus that causes the disease continues to be called the monkeypox virus.

The virus, however, can infect many other kinds of animals, including Gambian pouched rats, African dormice, squirrels, hedgehogs, and prairie dogs, among others. These animals can transmit the virus to humans, which is the most common form of transmission in endemic areas (in parts of Central and West Africa). But infected people can also transmit it to other people through direct skin contact or respiratory droplets in close proximity.

There are two clades (groups related by a common ancestor) of the monkeypox virus, referred to as the Clade I and the Clade II (subdivided into Clade IIa and Clade IIb). The 2022 global outbreak is caused by Clade IIb, which tends to cause milder illness and fewer deaths than Clade I.

Because mpox is closely related to smallpox, many of the treatments and vaccines for the latter disease are effective against mpox.

The monkeypox virus can get into a person’s body via the skin, the respiratory tract, and mucous membranes (moist tissue that lines the eyes, mouth, nose, anus, and genitals).

Mpox can be transmitted to people in several ways:

• Animal-to-person transmission. Infected animals can transmit the virus to humans via:
  • Bites and scratches.
  • Direct contact. The virus can be transmitted via contact with bodily fluids of infected animals, for instance while preparing meat. People can also become infected by eating raw or undercooked meat from an infected animal.

Prior to the 2022 outbreak, animal-to-person contact was the most common mode of transmission.

• Person-to-person transmission. It is thought that a person infected with the monkeypox virus is contagious from the onset of symptoms until the rash has scabbed over and all the scabs have fallen off. During this contagious period, the virus can be transmitted in a few ways:
  • Direct contact. Direct contact with the rash or bodily fluids of an infected person. This includes having sex, holding hands, hugging, kissing, and massages.
  • Respiratory droplets. The virus may be transmitted via respiratory droplets exhaled by an infected person. Evidence suggests that this mode of transmission requires prolonged close contact (e.g., being within six feet of an infected person for three or more hours).
  • Pregnancy. Pregnant people can pass the virus to the fetus via the placenta.

In the current 2022 outbreak, person-to-person transmission has been the predominant mode of transmission leading to worldwide spread. Prolonged and intimate skin contact or face-to-face contact (for large respiratory droplet transmission) is thought to be required for transmission.

• Transmission from surfaces and materials. Mpox may also spread through materials or surfaces that are contaminated with the virus. Contaminated materials may include bedding, clothing, or towels used by an infected individual or the cage or bedding of an infected animal.

It can take anywhere between 4 and 21 days for symptoms to appear after getting infected with the monkeypox virus.

Mpox symptoms can include:

• Fever
• Headache
• Muscle and joint pain
• Backache
• Chills
• Sore throat and cough
• Exhaustion
• Swollen (possibly painful) lymph nodes that are usually located in the body region(s) close to the rash
• Rash (usually painful and/or itchy)

The rash typically lasts for two to three weeks. It begins as flat spots on the skin which then transform into raised bumps. In turn, the bumps become blisters filled with clear fluid. After a day or two, the clear fluid turns into pus. After several days, the blisters crust and scab over. At this point, the rash can become itchy. The crusts and scabs eventually fall off as the skin heals.

The rash can develop on just about any part of the skin including the face, palms, soles of the feet, genitals, anus, and rectum. Rash can also occur in the mouth and eyes. The rash may be limited to one part of the skin, such as around the genitals or anus, or it may be widespread. Some people have only a few blisters, while others may develop hundreds of them.

In the 2022 outbreak, lesions predominantly located in or limited to the genital and/or anal regions have been common and have led to misdiagnoses of common sexually transmitted diseases. This is thought to be related to transmission among men who have sex with men in which mpox cases during the current outbreak have been predominantly seen. However, mpox cases are also identified in other population groups.

To diagnose mpox, doctors typically review the patient’s medical history, perform a physical exam, and run diagnostic tests.

During a medical history, patients will discuss their symptoms (including any flu-like illness), recent sexual contacts (in the current outbreak, the vast majority of cases occurred in men who have sex with men), and whether they have had contact with anyone who has or is suspected to have mpox. During the physical exam, lymph nodes will be checked for swelling and the skin will be examined for the presence of any rash.

Laboratory testing is necessary to confirm diagnosis. Specimens from skin lesions will be collected via a swab and then sent to a lab for genetic analysis to determine if monkeypox virus is present.

Treatment of mpox is mainly supportive, meaning it is aimed at reducing symptoms. Ibuprofen, naproxen, or acetaminophen can reduce fever and pain. The rash should be kept clean, dry, and uncovered (if not around others), and people should avoid touching skin lesions. Taking Epsom salt or baking soda baths may help soothe the rash. Lidocaine ointment and suppositories may relieve pain from rash, including on the genitals, anus, or rectum, while benzocaine or lidocaine sprays and mouthwashes can relieve pain caused by mouth lesions.

Antiviral medications and intravenous vaccinia immune globulin (VIGIV) may be used to treat people who develop more severe symptoms or who are at risk of more severe disease (e.g., immunocompromised people, pregnant women, children, and persons with skin disorders).

Antivirals that may be used to treat mpox include tecovirimat (known as TPOXX), brincidofovir (known as Tembexa or CMX001), and cidofovir. Tecovirimat is the medication of choice at this time because it is well tolerated with minimal adverse effects. While these drugs were developed to treat smallpox and other viral infections, they are also effective against mpox.

VIGIV is made from the blood plasma of people who have received a vaccinia (smallpox) vaccine.

There are two vaccines that are used to prevent an individual from getting sick with mpox.

• Jynneos. This vaccine is approved by the Food and Drug Administration (FDA) for the prevention of mpox and smallpox in people ages 18 and over. It contains a live attenuated (weakened) vaccinia virus that is related to the monkeypox virus but modified to prevent it from replicating. It requires two doses given four weeks apart. People are considered fully vaccinated two weeks after the second dose.
• ACAM2000. This vaccine is FDA-approved for the prevention of smallpox but is also effective against mpox. It requires one dose, and people are considered fully vaccinated four weeks after immunization. ACAM2000 is administered on the upper arm via multiple skin pricks with a bifurcated needle. The vaccine contains live vaccinia virus (a virus related to smallpox, but which causes milder illness) that causes a localized infection at the site of the needle prick. Within two to five days, a skin lesion forms. The lesion will scab over, and after the scab falls off, a scar remains. Because it can lead to serious complications in people with weakened immune systems, ACAM2000 is generally avoided in immunocompromised people. The vaccine cannot cause mpox or smallpox.

Vaccines can be given before exposure to the monkeypox virus to prevent illness. If they are given within four days of exposure, they may prevent symptoms from developing. They may reduce symptoms if they are given between four and 14 days of exposure.

Based on previous data, vaccination appears to be around 85% effective in preventing mpox. However, data from the 2022 outbreak will shed light on the level of protection afforded by vaccines.

In addition to getting vaccinated against the disease, people can reduce their risk of getting mpox by:

• Avoiding close contact (including sex) with people who have mpox symptoms
• Avoiding close contact with objects that have been touched by people with mpox symptoms
• Not sharing eating utensils or glasses with anyone who has mpox
• Regularly washing hands with soap and water or using an alcohol-based hand sanitizer
• Not touching or eating animals infected with the mpox virus

People who have mpox can reduce the chances of spreading the virus to others by:

• Self-isolating by staying home and away from others, including people in the household
• Using a separate bathroom in the household, if possible
• Avoiding contact with other people and pets (or other animals)
• Avoiding sex with other people
• Wearing a well-fitting face mask if around others
• Covering rash with clothing if around others
• Disinfecting surfaces touched by others

There are no specific, proven medications for treating mpox. Most people, however, have mild cases and recover from the disease within two to four weeks. In the 2022 outbreak, the mortality of proven cases of mpox has been very low (at around 0.03%) and may be lower, as there are likely thousands of mild cases that have been undiagnosed.

“The processes for recognizing and diagnosing the condition and managing exposures are complex,” says Dr. Azar. “In order to support Yale physicians in providing the highest quality care for patients with monkeypox, Yale and Yale New Haven Hospital have developed a specialized Monkeypox Pathway that provides detailed guidance on case recognition; specimen ordering and collection; isolation recommendations; exposure management and risk assessment; post-exposure prophylaxis, including vaccination; and treatment, including pain management, for patients in the community and those admitted to the hospital.”

These pathways are continually updated to reflect evolving CDC and Department of Health recommendations and requirements, he adds. “In this way, Yale ensures the highest quality care for patients with suspected and confirmed cases of monkeypox, and plays a significant role in the mitigation and containment of this outbreak in the New Haven area and beyond.”