Global public health emergency: On August 14, 2024, the World Health Organization (WHO) declared a public health emergency of international concern for the surge in clade I mpox activity in the Democratic Republic of the Congo and other countries in Africa.

Democratic Republic of Congo 2023 Outbreak (Clade I)

• A virulent mpox outbreak in the Democratic Republic of the Congo (DRC) involving clade I viruses began in 2023 and continues into 2024. A high proportion of cases have occurred in children aged younger than 15 years, with a case-fatality rate of 10% in infants and young children. Person-to-person transmission has occurred through household contact and within the health care setting. Individuals have also gotten mpox through contact with infected wild animals. The outbreak has also involved some sexual spread, including heterosexual transmission.
• Clinicians in the United States are advised to maintain a heightened index of suspicion for mpox in patients who have recently been in DRC or to any bordering country (Republic of Congo, Angola, Zambia, Rwanda, Burundi, Uganda, South Sudan, Central African Republic) and present with signs and symptoms consistent with mpox. There has been a case of clade Ib mpox in the United States in a traveler who had recently visited areas experiencing transmission. Sweden, Germany, India, Thailand, and Canada have also recorded imported cases of clade Ib mpox. The United Kingdom reported its first case of imported clade Ib mpox in October 2024, which resulted in local transmission to 4 household members. 

United States 2022 Outbreak (Clade IIb)

• As of March 5, 2024, there were 32 063 confirmed cases of mpox and 58 deaths in the United States caused by clade IIb. This outbreak was part of a larger 2022 global outbreak (99 518 cases) occurring in over 120 countries, territories, and areas, the vast majority of which did not historically report mpox infections.
• Per the US Centers for Disease Control and Prevention (CDC), after the peak of the 2022 mpox outbreak, when approximately 3000 cases per week were reported in the United States, cases declined sharply and remain significantly lower, with most new mpox cases occurring in unvaccinated individuals.
• In 2023, there were a total of about 1700 cases reported. In 2024, about 2300 cases have been reported as of October 7.
• Transmission continues to occur primarily among men who have sex with men (MSM), but any individual who has been in close, personal contact with someone who has mpox – regardless of age, sexual orientation, or gender identity – is at risk for contracting mpox. Domestic animals, pets, and wildlife in close contact with an infected individual may also be at risk for contracting illness.
• Refer to CDC Information for Clinicians for the most current information. See Diagnostic Pearls section for the CDC 2022 case definitions.

Postexposure prophylaxis: The CDC recommends that patients exposed to mpox should be vaccinated within 4 days of the exposure to prevent onset of disease. If given between 4 and 14 days after the date of exposure, vaccination may reduce symptoms but not prevent disease. See the CDC Interim Clinical Considerations for the latest guidelines and considerations for specific populations.

Pediatric patient considerations: Mpox virus infections in children and adolescents younger than age 16 years have been extremely rare, representing 0.002% of all US cases; none of the cases resulted in critical illness or death. Children aged 0-12 years typically acquired mpox after skin-to-skin contact with an infected household member during caregiving activities, and adolescents aged 13 years and older were most frequently exposed through male-to-male sexual contact. As of January 10, 2024, 64 cases have been reported in children 0-15 years old and 699 cases have been reported in adolescents / young adults 16-20 years old in the United States.

Immunocompromised patient considerations: Immunocompromised individuals, particularly people with advanced or inadequately treated HIV, are at risk for severe and prolonged illness and even death. An increasing proportion of cases have been identified among Black and Hispanic / Latino individuals, who are disproportionately affected by HIV.

About Mpox
Mpox is a rare zoonotic Orthopoxvirus infection that is clinically similar to smallpox.

There are genomic variants of mpox with differing mortality rates. The Central African (Congo Basin) clade is now referred to as clade I and is both more contagious and more severe with a reported mortality rate of around 10.6%. The West African clade is now referred to as clade IIa and is thought to be less severe with a mortality rate of about 3.6%. The virus responsible for the 2022 global outbreak is a clade IIb virus. Researchers have also confirmed the sexual transmission of clade I mpox virus in Africa, demonstrating that sexual transmission extends beyond clade IIb.

Clades I and IIa mpox begin with a prodrome of fever, headache, malaise, backache, lymphadenopathy, chills, nonproductive cough, and arthralgias followed 1-10 days later (usually by day 3) by the development of a papular, vesicular, then pustular eruption on the face, trunk, and extremities. Some patients also experience myalgias, nausea and vomiting, lethargy, sore throat, dyspnea, and sweats. Systemic symptoms are more prominent and severe in clade I disease. Illness typically lasts 2-4 weeks. Individuals who received smallpox vaccination were reported to develop milder cases.

Before the 2022 global outbreak, cases in the United States were primarily limited to laboratory workers, pet shop workers, and veterinarians. There were 2 US cases in 2021 (July and November), both from travelers returning from Nigeria.

In Africa, the disease has historically affected people who have hunted or eaten squirrels and other infected mammals. Animal species susceptible to mpox virus may include nonhuman primates, lagomorphs (rabbits), and some rodents. Predominant person-to-person transmission and prolonged chains of transmission were suspected in 1996 when 71 cases emerged in Katako-Kombe Health Zone, Kasai-Oriental, and Democratic Republic of the Congo, and again in 2003 in the Likouala region of Republic of the Congo. In order to sustain the disease in the human population, it was believed that repeated animal reintroduction of mpox virus was needed.

The 2022 outbreak of mpox is unique in several ways.

• Many cases have no clear connection to the larger clusters of cases and no clear history of associated travel.
• In the 2022 outbreak, it appears mpox is spreading through specific social and sexual networks, particularly among persons who identify as gay, bisexual, or MSM, although it is in no way limited to any specific population.

Community transmission seems to be occurring through close contact, ie, direct contact with skin lesions or bodily fluids, or indirect contact via contaminated clothing or linens, or exposure to large respiratory droplets. Twenty-one people in Spain are believed to have contracted mpox at a single tattoo parlor. Their presentations included cutaneous inflammation and necrosis local to their tattoo or piercing site.

Clinical features:
The incubation period of mpox is approximately 12 days (7-14 day range usually, but can be 5-21 days).

The clinical presentation of cases in the 2022 outbreak is distinct from prior descriptions of the illness. Notably, anogenital lesions (in some cases painful, in others painless), often without a prodrome, are being observed.

• Many patients have had no associated or preceding febrile illness, fatigue, or other systemic symptoms.
• The eruption that many of these patients develop does not begin on the face, hands, and legs and may not be widespread, nor are the lesions initially numerous. Many patients have presented with a small number of lesions (usually fewer than 10; in some cases 1 or 2) involving the genital or perianal region before the rash spreads to the extremities. These lesions can be, but are not always, quite painful and/or pruritic and may leave scarring.
• The classically described lymphadenopathy associated with mpox does not seem to be a requisite aspect of cases in this outbreak, with some patients having only a single swollen lymph node and some having no lymphadenopathy.
• Some patients present with proctitis or anorectal pain.
• Oropharyngeal symptoms have been reported (including pharyngitis, oral / tonsillar lesions, odynophagia, and epiglottitis) as have ocular symptoms (including conjunctivitis, keratitis, blepharitis, and lesions on the eyelids and the conjunctival mucosa). Oral mucosal lesions can occur without any other mucocutaneous symptoms.
• Asymptomatic cases may have occurred (and contributed to transmission) during the New York City 2022 outbreak per a serosurvey of 419 asymptomatic adults with no history of mpox infection or smallpox / mpox vaccination; 1 in 15 had antibodies to mpox, indicating the presence of asymptomatic infections.

In the 2022 outbreak, mpox may present in a form that can be very subtle and easily mistaken for many other conditions such as primary and secondary syphilis, genital herpes simplex virus (HSV), and chancroid, among others.

Transmission:
Human-to-human transmission occurs through close contact, ie, large respiratory droplets, direct contact with skin lesions or bodily fluids, or indirect contact via contaminated clothing or linens. The WHO notes that anyone who has had close physical contact with someone with mpox is at risk of contracting the virus, and there is a high likelihood that further cases with unidentified chains of transmission will be identified. MSM may be at higher risk for infection. Ocular symptoms may result from autoinoculation (ie, rubbing the eye after touching lesions elsewhere on the body).

All skin lesions may be infectious. Persons are thought to be infectious starting 1-4 days prior to the onset of symptoms (a UK study of more than 2700 people with confirmed mpox virus between May 6 and August 1, 2022, suggests that presymptomatic transmission [1-4 days before symptoms appear] occurred in around half of all cases [53%]). Patients should be considered infectious until crusts have fallen off and the underlying skin re-epithelialized.