News & Views — Monkeypox: What You Should Know

As if we are not all exhausted from dealing with COVID-19, now another infectious disease is making headlines — monkeypox. The good news is monkeypox is not as easily transmissible as COVID-19, but we thought it would be helpful to provide some background information, so that you are ready if questions arise.

Monkeypox: The biology

Monkeypox is a virus from the family, Poxviridae, and the genus, Orthopoxvirus. As such, it is related to other poxviruses, including variola virus (smallpox), vaccinia virus, cowpox, ectromelia virus (mousepox), camelpox virus, rabbitpox virus, Taterapox virus, volepox virus, raccoonpox virus, skunkpox virus, canarypox virus and Uasin Gishu disease virus, which affects horses. Notably, despite the similarity in name, chickenpox is not a member of this family of viruses. Chickenpox is caused by varicella-zoster virus, which is from the Herpesviridae family.

Monkeypox, and its familial relatives, are double-stranded DNA viruses. The DNA appears as a single linear genome and replicates in the cytoplasm, rather than the nucleus of cells. Although poxviruses are enveloped, they tend to be more hardy than other enveloped viruses, more often surviving on dry surfaces and appearing less susceptible to temperature or pH changes. Because of their envelope, they are considered susceptible to common disinfectants, but may be less susceptible to organic disinfectants. The U.S. Environmental Protection Agency (EPA) considers monkeypox to be a “tier 1-level emerging viral pathogen” (EVP). To check the effectiveness of different disinfectants against tier 1 EVP, use the EPA’s online list.

Most poxviruses infect animals. However, monkeypox is one of four types that can infect people. The others are smallpox, cowpox and vaccinia virus. Of these, smallpox was eradicated by 1980 due to successful vaccination campaigns. Cowpox tends to occur more frequently in Europe and parts of Asia. Vaccinia is more often found in South America, and until recently, monkeypox, most often in Africa.

Monkeypox can infect a variety of animal species, but its natural reservoir has not been identified. The virus was first discovered in 1958 during an outbreak in monkeys being used for research. It was not identified as a human pathogen until 1970 when an infant in the Democratic Republic of the Congo was infected. Monkeypox infection diagnoses were limited to Africa until 2003, when an outbreak emanating from infected pet prairie dogs occurred in the U.S. The pets, imported from Ghana, had been transported with Gambian pouched rats and dormice, which were identified as the likely source. More than 70 people were infected during that outbreak. Since then, most cases have resulted from travel to or from an area of Africa. However, in May 2022, cases not linked to travel or infected animals were identified in several countries outside of Africa.

Monkeypox: Transmission and symptoms

Historically, monkeypox infections occurred most often after exposure to an infected animal’s blood or bodily fluids, including from consuming poorly cooked meat from infected animals. However, person-to-person transmission has also been documented and is central to the recent outbreak. Infected individuals can spread the virus through contact with respiratory secretions, particularly after prolonged face-to-face contact or intimate interactions like kissing or oral sex. The virus can also be transmitted through direct skin-to-skin exposure to the rash or to other body fluids or indirectly through contaminated objects, like clothing or bed linens. Pregnant women are at risk of spreading the virus to their unborn babies through the placenta, and this type of exposure can result in a form of congenital monkeypox. However, babies can also be infected during delivery or by close contact after birth. In a few instances, people have been infected while hospitalized for other conditions. While sexual transmission has been hypothesized, the mechanism of transmission in this scenario remains uncertain.

Symptoms tend to appear between six and 13 days after exposure; however, the range of onset has varied from five to 21 days. The World Health Organization (WHO) describes two periods of infection:

• Invasion period — Lasting up to five days, this period is characterized by fever, headache, swelling of lymph nodes (lymphadenopathy), back pain, muscle aches and lack of energy. Notably, for purposes of differential diagnosis, lymphadenopathy is more likely during monkeypox infection than during chickenpox, measles or smallpox infections.
• Skin eruption period — Within one to three days of fever, the rash tends to appear. Most often it is more concentrated on the face and limbs (compared with the trunk) and may appear on the palms of hands and soles of feet. Lesions can also appear on mucosal membranes of the mouth, genitals and eye, including the cornea. The number of lesions an individual develops can be minimal or can occur in the thousands. In some cases, the lesions can overlap to cover large portions of the skin, which will eventually slough off.
  
  Typically, lesions begin with a flat base (macule) and progress to a slightly raised, firm version (papule), a clear fluid-filled version (vesicle), and a pus-filled version (pustule) before drying up and falling off. The progression can take about 12 days. Lesions may have a central depression and can be itchy, increasing the risk for secondary bacterial infections if individuals are scratching them.
  
  Pictures of monkeypox rashes are available on the CDC website and from links on the European Centre for Disease Prevention and Control (ECDC) website.

Of note, the Centers for Disease Control and Prevention (CDC) has indicated that not all patients will experience both sets of symptoms; some may only have the rash. Individuals usually recover within two to four weeks. Complications, in addition to secondary bacterial infections, can include swelling of the brain, bloodstream infection, dehydration, pink eye, corneal infection, vision loss and pneumonia. People with weakened immunity may be more susceptible to severe infection although the fatality rate is much lower than for smallpox. Recent cases are estimated to have a fatality rate of 3% to 6%. Historically, fatality rates ranged from 0% to 11%.

Monkeypox: Treatment

Because for most people infection is mild and resolves on its own, treatment most often takes the form of addressing symptoms and encouraging hydration. However, some patients at higher risk for severe disease may be recommended for additional interventions that are expected to be effective, although no treatments are currently approved specifically for use against monkeypox.

Antivirals

• Tecovirimat (TPOXX^®) is an antiviral known to be effective against smallpox.
• Cidofovir (Vistide^®) is an antiviral used to treat cytomegalovirus in patients with AIDS. Limited laboratory and animal study data suggest it is also effective against orthopoxviruses.
• Brincidofovir (CMX001, Tembexa^®) is an antiviral approved for treatment of smallpox.

Immune globulin

Vaccinia immune globulin intravenous (VIGIV) is licensed for the treatment of complications due to vaccinia vaccination or infections (except for isolated corneal infection caused by vaccinia).

The above treatment options, with the exception of Brincidofovir, are available from the strategic national stockpile and can be requested by local, state and territorial health authorities.

Monkeypox: Vaccination

Vaccines being used to prevent monkeypox are the same as those used to prevent smallpox, due to cross-reactivity of immune responses. As such, it is anticipated that individuals older than 50 who were vaccinated against smallpox as children may have some immunologic memory that could protect them against severe infection. However, the degree of long-lasting protection is uncertain, particularly since some previously smallpox-vaccinated individuals have been infected during this and previous monkeypox outbreaks. For these reasons, an individual’s previous smallpox vaccination status should not be taken into account when determining their eligibility for vaccination during the current outbreak.

Because of the delayed onset of symptoms following exposure, vaccination shortly after a known exposure can be effective. Taking this and current cases into account, current recommendations limit vaccination to the following groups:

• Known contacts identified via public health case investigations and contact tracing.
• Presumed contacts who had a sexual partner in the last 14 days who was diagnosed with monkeypox or who had multiple sexual partners in the last 14 days in a geographic area with known monkeypox cases.

Two vaccines are available in the U.S. Both are live, weakened viral vaccines designed originally to prevent human smallpox:

• JYNNEOS™ is made from a live vaccinia virus that has been changed so it cannot reproduce in people. The vaccine virus is grown in chick embryo cells and purified to make the final product. It is approved for use in adults 18 years of age and older and is given as two doses administered by subcutaneous route at least four weeks apart. Individuals should be considered immune two weeks after receipt of the second dose.
• ACAM2000^® is made from a live, weakened vaccinia virus. In this case the vaccine virus can reproduce itself after vaccination, so some individuals are not recommended to get this version, including people with heart disease, eye disease being treated with topical steroids, congenital or acquired immune deficiency disorders, current or previous atopic dermatitis or eczema and pregnant women.
  
  The vaccine virus is grown in monkey kidney cells and purified to make the final product. It is approved for those 12 months of age and older and is administered as a single dose by percutaneous route (scarification). Scarification involves delivering a drop of reconstituted vaccine on the skin using a bifurcated needle and then administering 15 jabs in the droplet (area should be no larger than 5 millimeters). The jabs should be sufficient to puncture the skin, resulting in a drop of blood. If the vaccine was properly administered, a lesion (blister) will develop at the vaccination site. The lesion can take up to six weeks, or slightly longer, to heal. Individuals should be considered immune four weeks after receipt of the vaccine.
  
  Importantly, because this vaccine virus reproduces at the inoculation site, vaccinated individuals may be able to spread the virus to others if they come into contact with the lesion either directly or indirectly through objects that have touched the lesion. As such, recipients should be advised to keep the vaccination site clean and covered until the lesion heals.

Recipients of both versions may experience pain, redness or swelling at the injection site. Those who receive ACAM2000 may also experience fever, rash, swelling of lymph nodes or complications of inadvertent inoculation at other sites (e.g., brain or spinal cord swelling, brain damage, vaccinia disease or skin infections, Stevens-Johnson syndrome, eczema vaccinatum, eye infection, blindness, or fetal death). About 5 or 6 people out of 1,000 who receive ACAM2000 may also experience myocarditis or pericarditis. The risk for myocarditis or pericarditis following receipt of JYNNEOS is not currently known. However, due to the risk of myocarditis following receipt of COVID-19 mRNA vaccines, the CDC recommends that individuals wait four weeks after getting an orthopox vaccine (either ACAM2000 or JYNNEOS) before getting a COVID-19-based mRNA vaccine. This recommendation is particularly relevant for teen and young adult males. On the other hand, if a person is recommended for orthopox vaccination due to an outbreak, it should not be delayed due to recent receipt of a COVID-19 mRNA vaccine. Finally, individuals inadvertently inoculated by exposure to a vaccine recipient’s lesion (following receipt of ACAM2000) may also experience these adverse events or complications.

As of July 2022, supplies of JYNNEOS are limited in the U.S., but additional quantities are expected in the coming weeks. Ample supply of ACAM2000 is available but given the restrictions on its use and the chance to spread vaccine virus to others, JYNNEOS is the preferred product.

Additional resources

• CDC monkeypox resources
• WHO monkeypox resources
• ECDC monkeypox resources
• Info about rashes from the Vaccine Education Center (including photos) webpage | booklet | poster (Note: Spanish versions of the booklet and poster are also available on the VEC website.)
• JYNNEOS package insert
• ACAM2000 package insert