Clades I and II mpox classically 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.
Mpox clade IIb was part of a global outbreak in 2022 occurring in over 120 countries, territories, and areas, the vast majority of which did not historically report mpox infections. The clinical presentation of cases since the 2022 outbreak has been distinct from prior descriptions of the illness. Notably, anogenital lesions (in some cases painful, in others painless), often without a prodrome, are more prevalent. The eruption often 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 involving the genital or perianal region before the rash spreads to the extremities. Lymphadenopathy may or may not be present. Oropharyngeal and ocular symptoms have been reported. The infection may present in a form easily mistaken for other conditions such as primary and secondary syphilis, genital herpes simplex virus (HSV) infection, and chancroid, among others.
United States
Clade II mpox:
- Clade II mpox is still circulating at low levels in the United States. 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 is at risk for contracting mpox. Travel-associated cases have also been reported.
- 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.
- 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.
- Per the Centers for Disease Control and Prevention (CDC), since November 2024, there have been 10 reported cases of clade I mpox in the United States in people who had recently traveled to areas associated with an outbreak in Central and Eastern Africa or who were linked to people who traveled from these areas. The risk posed by the clade I mpox outbreak to most people within the United States remains low.
- Clinicians in the United States are advised to maintain a heightened index of suspicion for mpox in patients who have recently been in Central or Eastern Africa, specifically, Democratic Republic of the Congo (DRC) or 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. Additional countries that have experienced sustained human-to-human transmission include Ethiopia, Kenya, Malawi, Mozambique, and Tanzania.
Sierra Leone 2025 Outbreak (Clade IIb)
- On January 13, 2025, Sierra Leone declared a public health emergency. It was declared over on January 16, 2026. It was the largest mpox outbreak ever recorded in the country, with over 5000 cases and 60 deaths.
- The outbreak mainly affected individuals aged 20-34 years, including sex workers. Genital lesions were reported to be common, suggesting sexual transmission, as seen in clade IIb outbreaks in nonendemic countries since 2022.
- A virulent mpox outbreak in the DRC involving clade I viruses began in 2022 and continues into 2026. 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 contracted mpox through contact with infected wild animals. The outbreak has also involved some sexual spread, including heterosexual transmission.
- Per the CDC, since January 1, 2024, the DRC and several neighboring countries in Central and Eastern Africa have confirmed through laboratory testing more than 46 000 mpox cases and more than 200 deaths.
Clinical features:
- The incubation period of mpox is approximately 12 days (7-14 day range usually, but can be 5-21 days).
- Many patients have 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.
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.
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