Monkeypox (Mpox)

Figure 1: Monkeypox virus, brick-shaped negative stained virus grown in tissue cultures, visualized by electron microscopy; SOURCE: CDC/Cynthia S. Goldsmith, Inger K. Damon, and Sherif R. Zaki

• Monkeypox is a viral disease that produces pox-like lesions on the skin. It is closely related to smallpox but is not nearly as deadly as smallpox.
• The history of monkeypox is new (1958), and medical professionals diagnosed the first human monkeypox cases and differentiated them from smallpox in the early 1970s.
• Monkeypox virus (MPXV) causes monkeypox. The majority of cases are transmitted from animals (rodents) to humans by direct contact.
• Monkeypox is contagious. Person-to-person transfer, probably by droplets, can occur infrequently.
• Monkeypox can spread to humans from an infected animal through an animal bite or direct contact with the animal's lesions or bodily fluids.
• Monkeypox can spread to humans. Early symptoms include fever, headache, muscle aches, backache, swollen lymph nodes, a general feeling of discomfort, and exhaustion.
• Risk factors for monkeypox include close association with African animals (usually rodents) that have the disease or caring for a patient who has monkeypox.
• During the first few days, symptoms are nonspecific and include fever, nausea, and malaise. After about 4-7 days, rash/lesions (fluid-filled pustules, papules) develop on the face, trunk, and extremities that ulcerate, crust over, and begin to clear up after about 14-21 days, and lymph nodes enlarge. There may be some scarring.
• The diagnosis of monkeypox is often made presumptively in Africa by the patient's history and the exam that shows the pox lesions, however, a definitive diagnosis is made by PCR, ELISA, or Western blotting tests that are usually done by the CDC or some state labs. A definitive diagnosis is important to rule out other possible infectious agents like smallpox.
• Treatment may consist of immediate vaccination with the smallpox vaccine because monkeypox is so closely related to smallpox and thus cross-protective. Treatment with an antiviral drug or human immune globulin has been done.
• In general, the prognosis for monkeypox is good to excellent as most patients recover. The prognosis may decrease in immunocompromised patients, and patients with other problems such as malnutrition or lung disease may have a poorer prognosis.
• Monkeypox is preventable as long as people avoid direct contact with infected animals and people. Vaccination against smallpox seems to afford about an 85% chance of avoiding the infection. There is no commercially available vaccine specifically for monkeypox.
• Monkeypox can be fatal in up to 2% of cases.
• Research is ongoing to study antivirals, genetics, and rapid tests for monkeypox.
• The World Health Organization renamed "monkeypox" as "mpox" in November 2022.

Figure 2: Picture of the pustules/papules of characteristic monkeypox rash; SOURCE: World Health Organization (WHO)/Brian W.J. Mahy, BSc, MA, PhD, ScD, DSc

Monkeypox is a relatively rare disease that was first detected in monkeys in Africa in 1958 and resembles smallpox in terms of the skin lesions (pox) seen in humans as part of the physical findings and also because the cause is a virus that is closely related to the smallpox (variola) virus. Monkeypox, smallpox, cowpox, and vaccinia viruses all belong to the same family of viruses, the Poxviridae. Monkeypox belongs to the same genus (Orthopoxvirus) as smallpox. The disease is different from smallpox.

Monkeypox may be transferred from animals to people or person to person and has far less mortality (death rate) than smallpox had. The case-fatality rate (death rate) for monkeypox virus infection in Africa varies from about 1%-15% and about 15%-20% in children. Monkeypox virus is endemic in rodent populations in Africa.

Smallpox did not infect any endemic animal population and only infected humans. The press and bloggers have occasionally tried to link monkeypox to other diseases such as mad cow disease, Ebola, leprosy, yellow fever, and other viral and immunological diseases, but there is no scientific evidence for this.

Monkeypox has a relatively recent history. People first discovered it in monkeys in 1958, although a "vesicular disease in monkeys" was described in the 1860s. The disease, and eventually the causative virus, was named monkeypox because the lesions (pox) seen in monkeys developed like other known pox-forming diseases (pustules that eventually break open, ulcerate, crust over, and some pox form scars in the skin). Later studies showed the "monkeypox" virus was actually sustained endemically in African rodents. It was not until 1970 in Africa (Zaire, now the Democratic Republic of Congo also termed Republic of the Congo, DRC, and Congo) that a 9-year-old boy (who developed smallpox-like lesions) was the first person to eventually be diagnosed with monkeypox. This situation initially caused concern that smallpox may also have an animal reservoir or endemic population that would make eradication of smallpox impossible. Fortunately, this was not the case because monkeypox was found to be a different species of poxvirus, and smallpox was eradicated from the human population by vaccinations in 1979 (currently, only a few research labs have access to smallpox viruses). Monkeypox is now the major Orthopoxvirus (also termed orthopox) that infects humans and fortunately, not frequently. However, vigilance is warranted, as there have been several outbreaks of monkeypox since the 1970s. Although most have occurred in Africa (mainly western and central Africa), there was an outbreak in the U.S. in 2003. This apparently happened when an animal distributor either housed or transported monkeypox-infected African rodents (Gambian rats) with prairie dogs that people later purchased as pets, became "sick," and transmitted the disease to their owners. Other animals like the rope squirrel (Funisciurus anerythrus) and the sun squirrel (Heliosciurus rufobrachium) may transmit the virus to humans in Africa.

In 2017, an outbreak of monkeypox began in Nigeria. This large outbreak is thought to be triggered by river flooding that has caused infected wild animals (especially rodents and monkeys) to more closely associate with humans, thus spreading this zoonotic (transmitted to humans from animals) disease. From 2017 to the present, Nigeria has recorded 446 cases. In September 2018, Dr. Beadsworth in England reported treating three people with monkeypox who had visited Nigeria. The three patients likely were exposed to the virus while visiting Nigeria. On July 15, 2021, a person was diagnosed with monkeypox in Dallas, Texas, and the CDC confirmed this. He traveled by air from Nigeria to Atlanta, Georgia, and then flew on to Dallas, Texas. Both airlines he used had required masks, so the CDC thinks the risk is low for transmission of the disease. Another case was diagnosed in Maryland in 2021.

The current outbreak (May 2022) has spread to non-endemic countries according to the World Health Organization (WHO). The countries include Australia, Belgium, Canada, France, Germany, Italy, Netherlands, Portugal, Spain, Sweden, the United Kingdom (Britain), and the USA. Most cases (about 21-30 per country) are in Spain, Portugal, and the United Kingdom. In addition, Israel, Switzerland, Denmark, and the Canary Islands have reported at least one confirmed case. Other countries have yet to document their cases. The U.S. has two to three presumptive cases identified in travelers to Florida with one confirmed; Massachusetts, New York, Utah, and Washington all have a least one documented case.

An Orthopoxvirus named monkeypox causes monkeypox. The viruses are oval brick-shaped viruses that have a lipoprotein layer with tubules or filaments that cover the viral DNA. There are many members of this viral genus, including such species as variola (smallpox), cowpox, buffalopox, camelpox, rabbitpox, and others. Most species infect a particular animal species but occasionally may infect other mammals.

Transmission of monkeypox is usually by direct contact with infected animals or possibly by eating poorly cooked meat from an infected rodent or monkey. Cutaneous or mucosal lesions on the infected animals are a likely source of transmission to humans, especially when the human skin is broken due to bites, scratches, or other trauma -- are likely sources of virus infection. Human-to-human transfer, probably by infected respiratory droplets, is possible but is not often documented. Direct skin contacts with lesions, body fluids, and contaminated bedclothes or clothing are the most likely transmission methods. One study suggested that only about 8%-15% of infections occurred through human-to-human transmission among close family members.

Monkeypox is a relatively uncommon disease. Risk factors include animal bites and scratches from infected animals (mainly African rodents or monkeys) or from other rodents (like prairie dogs) that have had contact with African animals infected with the virus. People should avoid eating any meat from such animals is advised.

Recent studies have shown that monkeypox can infect several species of mammals, even though the species had never been associated with the virus in their normal environment. Reduce or prevent the person-to-person transfer, although infrequent, by avoiding direct physical contact with the patient and having the patient's caregivers wear gloves and face masks. Avoid skin contact and clothing with potentially infected people. In Spain, one outbreak (about 30 cases) was traced to a Madrid sauna that is popular with gay men. However, monkeypox is not considered a sexually transmitted disease; it may occur more frequently in sexually active groups because of skin-to-skin contact during sex.

• The first symptoms that occur are nonspecific -- fever, chills, headache, muscle aches, sweating, malaise, fatigue, exhaustion, and some patients may develop a cough, nausea, and shortness of breath.
• About two to four days after fever develops, a rash with papules and pustules develops most often on the face and chest, but other body areas may eventually be affected, including mucus membranes inside the nose and mouth.
• These skin and mucus membrane pox lesions can ulcerate, crust over, and then begin to heal in about 14-21 days.
• In addition, lymph nodes usually swell (lymphadenopathy) during this time.
• Some pox lesions may become necrotic and destroy sebaceous glands, leaving a depression or pox scar that, with monkeypox, may gradually become less pronounced over a few years.
• The toxemia that was seen with smallpox is not seen with monkeypox.

The incubation period (time from exposure to first symptoms) is about 7-14 days. The first symptoms include fever, headache, muscle pains, swollen lymph nodes, and feeling tired. Swollen lymph nodes help distinguish monkeypox from smallpox.

The infected person is not contagious during the incubation period. However, human cases can be contagious as soon as symptoms develop. The person is contagious until all scabs from the pox lesions fall off. Consequently, the person is usually contagious for about 4-5 weeks.

The history (especially association with rodents or other animals) and physical exam (presence of pox lesions) are presumptive evidence for a diagnosis of monkeypox. Caution is advised. Infectious disease consultants and the Centers for Disease Control and Prevention (CDC) personnel should be notified because this infection may represent two additional problems.

• First, in the U.S. or other countries, it may likely indicate an outbreak of monkeypox, and informed health authorities may help to identify the source of the infection and prevent its spread.
• The second problem is unlikely but far more serious; the early symptoms may represent a biological warfare or terrorist attack with smallpox that is mistakenly identified as monkeypox.

Consequently, a definitive diagnosis of this viral disease, outside of Africa, and especially in developed countries where monkeypox is not endemic, is urged. Most laboratories do not have the reagents to do this testing, so state labs or the CDC will need to process the samples to establish a definitive diagnosis. These tests are based on detecting antigenic structures (usually from skin or pox samples or occasionally serum) specific to either the monkeypox virus or immunoglobulin that reacts with the virus. PCR (polymerase chain reaction), ELISA techniques (enzyme-linked immunosorbent assay), or Western blotting tests (immunoblotting) are the main tests used.

The CDC recommends the following:

• A smallpox vaccination should be administered within 2 weeks of exposure to monkeypox.
• The FDA approved the Jynneos vaccine for the immunization of adults that are at high risk for smallpox or monkeypox (September 2019).
• Cidofovir (Vistide), an antiviral drug, is suggested for patients with severe, life-threatening symptoms.
• Vaccinia immune globulin may be used, but its efficacy of use has not been documented.

For severe symptoms, supportive measures such as mechanical ventilation may rarely be needed. Consultation with an infectious-diseases expert and the CDC is recommended.

The usual prognosis of patients with monkeypox is good to excellent. Many patients have mild symptoms. However, patients with immune or other compromised health problems (malnutrition, lung problems) may develop complications of secondary bacterial infections, pneumonia, and dehydration.

Older estimations of a 10% death rate were published, but in the last 10-15 years, this has been revised to less than 2% of infected individuals, with the worst cases originating from animal-to-human infection, not person to person.

Monkeypox can be prevented by avoiding eating or touching animals known to acquire the virus in the wild (mainly African rodents and monkeys). The person-to-person transfer has been documented. Patients who have the disease should physically isolate themselves until all of the pox lesions have healed (lost their crusts), and people who are caring for these patients should use barriers (gloves and face masks) to avoid any direct or droplet contact. Caregivers should obtain a smallpox vaccination (see below).

Because smallpox and monkeypox are so closely related, studies have suggested that people vaccinated against smallpox have about an 85% chance of being protected from monkeypox. Consequently, the CDC recommends the following:

• Patients with depressed immune systems and those who are allergic to latex or smallpox vaccine should not get the smallpox vaccine.
• Anyone else who has been exposed to monkeypox in the past 14 days should get the smallpox vaccine, including children under 1 year of age, pregnant women, and people with skin conditions.

There is no commercially available vaccine designed specifically for monkeypox.

Research is ongoing on the monkeypox virus. For example, prairie dogs are being used as animal models to test the effectiveness of vaccinations. Several studies are using animal models to test the effectiveness of several antiviral drugs to reduce or eliminate symptoms in experimental infections. Because of the close relationship of smallpox to monkeypox, genetic comparison and genetic alteration studies are likely to be available in the future, along with more rapid detection tests.

Additional information about monkeypox can be found at these websites:

"Multi-country monkeypox outbreak in non-endemic countries," May 21, 2022, WHO

"Monkeypox," Centers for Disease Control and Prevention

"Monkeypox," Medscape.com