natalensis), tiny fat mice (Steatomys parvus) and shrews (Crocidura spp.) in Zambia. Prairie dogs seem to be very susceptible to monkeypox. Many of the prairie dogs exposed to monkeypox became infected during the outbreak in the U.S., and mortality rates as high as 60% have been reported after experimental inoculation. Another study reported 50-75% mortality in rope squirrels (Funisciurus anerythrus) inoculated with a Congo Basin strain. However, some species of rodents might be relatively resistant to clinical signs. During the outbreak in the U.S., monkeypox virus was found in one Gambian giant pouched rat that died soon after arrival, but another animal had a very mild illness, and orthopoxvirus antibodies were found in 12 of 18 healthy individuals after the outbreak. Limited experimental evidence also suggests that Gambian pouched rats are less susceptible than rope squirrels or prairie dogs. The Congo Basin clade seems to be more virulent than West African viruses for nonhuman primates and some rodents(e.g., prairie dogs, squirrels), although a West African virus was reported to be at least as virulent for Gambian pouched rat as the Congo Basin strain. Infections in Humans Incubation Period Reported incubation periods in humans range from 7 to 24 days, with a mean of 12 days in Africa and 14.5 days during the outbreak in the U.S. Clinical Signs Human monkeypox resembles smallpox, with a rash and constitutional signs, but the symptoms are generally milder and, unlike smallpox, the lymph nodes are usually (though not always) enlarged. Most often, the illness begins with nonspecific, flu–like symptoms that may include malaise, fever, chills, headache, sore throat, myalgia, backache, fatigue, nausea, vomiting and a nonproductive cough. Lymphadenopathy can be regional or generalized, and most often affects the submandibular, postauricular, cervical and/or inguinal lymph nodes. Most patients develop a rash one to several days after they begin to feel ill, though there have been instances where patients noticed a few skin lesions (e.g., at the site of an animal bite or scratch, or in the groin) shortly before they felt unwell. Skin lesions are usually concentrated on the extremities (including the palms and soles), but they can also be seen on the head and torso, as well as the mucous membranes and genitalia. They vary in number from less than 25 to more than a hundred, and may become confluent in severe cases. As in animals, skin lesions usually begin as macules and papules, which develop into vesicles and pustules (“pocks”), umbilicate, form scabs and are eventually shed. During the outbreak in the U.S., some pustules had prominent erythematous flares. Such flares have not been noted in African cases, possibly because most affected people have darker skin. The skin lesions usually resolve within 14 to 21 days. Residual varioliform scarring, with hypopigmented and/or hyperpigmented skin lesions, may be a sequela in some cases. Severe scarring, as seen in smallpox, is rare. Some patients also have ocular signs including conjunctivitis, or more rarely, keratitis or corneal ulceration. Respiratory complications including bronchopneumonia, coagulation disorders, and rare cases of encephalitis or multiorgan failure have also been reported. Secondary bacterial infections can occur, and may lead to sepsis. Pregnant women may abort or give birth to an infected fetus. One fetus infected in utero was stillborn, with cutaneous maculopapular skin lesions and severe hepatic involvement; another had skin lesions and was born prematurely but alive. At least one mildly affected pregnant woman gave birth to a full-term, healthy child. Most patients recover in 2-4 weeks, but deaths are possible, especially in people infected with the Congo Basin clade or immunosuppressed individuals infected with either clade. Subclinical and very mild cases have also been reported. Monkeypox © 2004-2022 www.cfsph.iastate.edu page 5 of 9 Diagnostic Tests Monkeypox can be tentatively diagnosed if the characteristic skin lesions are present and there is a history of exposure; however, clinical cases can resemble chickenpox and may be difficult to distinguish clinically from the latter disease. Tests to isolate monkeypox virus or identify its nucleic acids and antigens are similar to those used in animals. At least one rapid point-of-care test, a lateral flow assay for viral antigen, is commercially available. In humans, monkeypox virus can be found in skin lesions (e.g., in scabs or material from vesicles) or throat and nasopharyngeal swabs. Serology may be helpful in some cases, although crossreactions with other orthopoxviruses complicate the interpretation of serological tests. An enzyme-linked immunosorbent assay (ELISA) can be used to detect orthopoxvirus-specific IgM. A rising IgG titer in paired samples is also suggestive. Cross-adsorbed virus neutralization, immunofluorescence or hemagglutination inhibition assays, as well as immunoblotting (Western blotting), can be used to distinguish reactions to monkeypox virus and smallpox virus, although some of these assays are not always easy to interpret. A specific ELISA that may detect monkeypox antibodies in people vaccinated for smallpox has been reported in the literature. Treatment Treatment of monkeypox is mainly supportive. Tecovirimat (chemical agent ST‐246), which is