Poxviruses that infect humans range from the life-threatening smallpox virus to the highly contagious but benign molluscum contagiosum virus . As of May 2022, hundreds of cases related to another poxvirus, monkeypox, have been reported in more than 30 countries around the world, including the US.
The monkeypox virus was first isolated in 1958 from monkeys at the Statens Serum Institut in Copenhagen, Denmark, hence its name; However, the natural host of monkeypox virus also includes rope squirrels, tree squirrels, Gambian rats, and dormice. As with many zoonoses, this poxvirus is incidentally transmitted to humans when they encounter infected animals. The first known human case of monkeypox was recorded in 1970 in the Democratic Republic of the Congo.
Before 2022, imported human cases have rarely been observed outside the African continent. In 2003, cases of monkeypox were reported in the US when a shipment of infected Gambian rats subsequently infected prairie dogs housed in the same facility and eventually infected 71 humans who adopted these animals as pets.
In 2018, 2 people who had traveled to Nigeria brought the disease to the UK and a secondary monkeypox infection was documented in a healthcare worker. Over the past 5 years, hundreds of cases of monkeypox have been reported in Nigeria, with many cases among men, some with genital lesions, suggesting human-to-human transmission through sexual contact.
The monkeypox outbreak of 2022
The current outbreak illustrates the easy transmissibility from person to person through direct and intimate contact with lesions containing the virus.
Since early May 2022, cases of monkeypox have been reported in several countries where the disease is not endemic. As of June 9, 2022, more than 1,350 laboratory-confirmed cases of monkeypox have been reported in 31 non-endemic countries worldwide with approximately 60% reported in 3 countries: Portugal, Spain, and the United Kingdom. As of June 9, 2022, the US Centers for Disease Control and Prevention (CDC) reported 45 cases in 15 states and the District of Columbia.
Most reported cases have no link related to travel to an endemic country, and most cases have occurred among men who have sex with men, increasing the possibility of sexual transmission . While monkeypox is not a sexually transmitted infection in the typical sense, it can be easily transmitted during sexual and intimate contact. Inoculation of the virus into the skin and mucosal surfaces occurs through direct, sexual, or skin-to-skin contact, and may even include transmission through fomites such as towels, bedding, and sex toys.
Viral clades and pathology
There are 2 known distinct clades of monkeypox virus, one endemic to West Africa and one to the Congo Basin. Historically, the Congo Basin clade has caused more severe disease and is thought to be more transmissible. The current monkeypox outbreak appears to be caused by the West African clade.
Monkeypox pathology, like all poxviruses, is characterized by prominent intracytoplasmic eosinophilic inclusions in epithelial cells. Other changes seen in the epidermis may include ballooning degeneration, keratinocyte necrosis, and hyperplasia. The dermis presents lymphocytic inflammation and, as ulceration occurs, there is infiltration by neutrophils, eosinophils and multinucleated giant cells. There is also inflammation around the vessels (vasculitis).
Clinical symptoms
Monkeypox has a long incubation period ranging from 5 days to 3 weeks. Patients usually present with fever, chills, fatigue, headache, muscle aches, sore throat, lymphadenopathy, and skin lesions.
Skin lesions progress from macules and papules to vesicles and pustules that ulcerate and form scabs before healing over several weeks. Skin lesions usually occur in crops. The initial lesions are usually at the site of inoculation, which may explain why in the current outbreak the lesions have been located on or near the genitals or anus.
Most of the time, monkeypox infection is self-limited and usually lasts 2 to 4 weeks.
Complications can include pneumonia, encephalitis, and eye infections, which primarily occur in children under 8 years of age, pregnant people, or immunocompromised people. The mortality rate is estimated between 1% and 11%.
During the 2003 US outbreak, a family that had acquired an infected prairie dog demonstrated the spectrum of the disease: a 6-year-old boy was hospitalized with encephalitis; the child’s mother was symptomatic and had multiple skin lesions; and the child’s father, who had been vaccinated against smallpox, had only 2 skin lesions and mild flu-like symptoms.
Diagnosis
The differential diagnosis of monkeypox includes other poxviruses and herpesviruses, including chickenpox.
The clinical diagnosis of monkeypox must be confirmed by laboratory methods, which are currently only available at state public health departments, where polymerase chain reaction is performed and positive cases are sent to the CDC for confirmation of the specific clade.
Specimens for monkeypox diagnosis should be collected with a nylon, polyester, or Dacron swab and preferably obtained from an open skin lesion. The swab sample should then be placed in a dry, sterile container and kept refrigerated or frozen until testing. Additional details can be found on the CDC and state health laboratory websites.
Prevention
Preventing monkeypox infection can be challenging for people who have close contact with an infected patient . Avoiding direct contact with skin lesions or materials used by monkeypox patients (such as clothing, bedding, and towels) is essential to reduce the risk of infection.
Doctors caring for patients with skin lesions should wear personal protective equipment including gown, gloves, eye protection, and a tight-fitting N95 mask .
A patient with suspected or confirmed monkeypox infection should be masked immediately, cover the lesions with a gown or sheet, and be placed in isolation in a single-person room. No special air management is required, but if a patient is admitted to the hospital for care, she should be placed in a negative pressure room, if available.
For environmental infection control, smallpox vaccination is believed to provide up to 85% cross-protection against monkeypox, although the duration is unknown. Some public health experts have suggested that the resurgence of monkeypox is due in part to the end of routine smallpox vaccination after the disease was eradicated in 1980.
There are currently 2 licensed vaccines available to prevent smallpox in the US: ACAM2000 and JYNNEOS (also known as Imvamune or Imvanex), which is a live, non-replicating, modified vaccinia Ankara virus vaccine. While JYNNEOS is the only vaccine currently approved by the US Food and Drug Administration (FDA) to prevent monkeypox, the Advisory Committee on Immunization Practices recommends that people with occupational exposure to orthopoxviruses ( e.g., researchers working with monkeypox virus samples) receive ACAM2000 or JYNNEOS vaccine as pre-exposure prophylaxis.
Post-exposure vaccination with JYNNEOS may also be administered to patients who have had close contact with a person infected with monkeypox virus. The CDC recommends vaccination within 4 days of exposure to prevent illness or up to 14 days after exposure to reduce the severity of illness. More than 36,000 doses of the JYNNEOS vaccine are currently in the US Strategic National Stockpile. Although the CDC has recommended that the JYNNEOS vaccine be offered to close contacts of monkeypox patients, it is currently not easily accessible. this vaccine.
Treatment
Treatment of monkeypox is mainly symptomatic , as there is currently no specific antiviral treatment. People with severe illness, immunocompromised patients, children younger than 8 years, and pregnant people should be considered for antiviral treatment after consulting with CDC.
There are currently 2 antiviral medications that can be used for monkeypox infections: tecovirimat and brincidofovir . Tecovirimat prevents viral envelope formation by inhibiting p37, a highly conserved protein in all orthopoxviruses. Tecovirimat was approved by the FDA for the treatment of smallpox in 2018, and the CDC has an expanded access investigational new drug (EA-IND) protocol that allows its use in orthopoxviruses other than smallpox, like the monkeypox virus.
Brincidofovir is a prodrug of cidofovir, a drug approved for the treatment of cytomegalovirus (CMV) retinitis in patients with AIDS. No serious renal toxicity or other serious adverse events have been observed with brincidofovir during the treatment of CMV infections, so it may have a better safety profile than cidofovir, but clinical experience is limited. Brincidofovir was approved by the FDA for the treatment of smallpox in 2021 and, as with tecovirimat, the CDC has an EA-IND allowing its use with the monkeypox virus. However, brincidofovir is currently not available in the US Strategic National Stockpile.
Intravenous vaccinia immunoglobulin ( VIGIV) may be considered for patients with severe monkeypox infection or as prophylaxis in exposed individuals with T-cell immunodeficiency, for whom smallpox vaccination is contraindicated. However, it is currently unknown whether these people with monkeypox infection will benefit from treatment with antiviral agents or VIGIV.
Conclusions Monkeypox virus is a highly contagious orthopoxvirus that is currently causing a global outbreak, primarily among men who have sex with men. Controlling this growing international outbreak will require careful coordination between public health officials, clinicians, and the community to disseminate information, obtain appropriate diagnostic testing, implement contact tracing, and ensure that affected individuals and their contacts have access to medical care. |
