enlargement and/or mottling of the liver, orchitis, and multifocal necrotizing lesions in various organs and tissues including the spleen, liver, colon, thymus, brown fat, uterus or vagina. Hemorrhages were noted in the upper gastrointestinal tract, nasal cavity, gall bladder and brain of intranasally inoculated dormice, and in the lungs of experimentally infected ground squirrels, together with pulmonary edema. Diagnostic Tests The characteristic skin lesions and histopathology are suggestive, but can be caused by other diseases. If the animal has not been exposed to other orthopoxviruses, monkeypox can be tentatively diagnosed by detecting orthopoxvirus virions with electron microscopy or orthopoxvirus antigens by immunohistochemistry. The diagnosis can be confirmed by virus isolation or assays for genetic material, such as PCR. Monkeypox virus may be detected in skin lesions or samples from affected organs at necropsy, and sometimes in conjunctival swabs or oral and nasal secretions (e.g., oropharyngeal swabs). One study found that the liver contained particularly large amounts of virus in dormice. The virus has also been detected in the blood, urine and/or feces of some animals. Monkeypox virus can be recovered in various cell lines including Vero cells, and may be specifically identified with PCR followed by restriction fragment–length polymorphism (RFLP) analysis or sequencing. Monkeypox-specific PCR assays are available in some laboratories, and a DNA oligonucleotide microarray can identify this virus rapidly and specifically. PCR can also be performed directly on clinical samples. Loop-mediated isothermal amplification (LAMP) assays for the Congo Basin and West African strains have been developed. Serology is mainly used for surveillance in animals. Antibodies to other orthopoxviruses can cross-react with monkeypox virus. Treatment Treatment is supportive, but may not be advisable or allowed in some situations. During the 2003 outbreak in the U.S., the CDC recommended that all animals with suspected monkeypox be euthanized, in part to prevent zoonotic infections. Nonhuman primates are not necessarily euthanized during outbreaks in facilities. Control Disease reporting Veterinarians who encounter or suspect monkeypox should follow their national and/or local guidelines for disease reporting. In the U.S., state or federal authorities must be notified immediately. Prevention As a result of a monkeypox outbreak in 2003 that was caused by imported exotic pets, the U.S. banned the importation of six types of African rodents – squirrels in the genera Heliosciurus and Funisciurus, dormice, Gambian giant pouched rats, brush-tailed porcupines (Atherurus sp.), and striped mice (Hybomys sp.). This ban applies to these animals whether they were born in Africa or on another continent. In addition, prairie dogs can no longer be captured from the wild for use as pets. Exceptions to these restrictions are allowed, by permit, for organizations such as zoos and scientific institutions. Similarly, some other countries and governing bodies such as the E.U. banned the importation of prairie dogs from the U.S. and some rodents from Africa. Good infection control measures, including the isolation of new animals, help prevent outbreaks in primate facilities and facilities that import exotic pets. Because infections have been reported in Asian monkeys mixed with primates from Monkeypox © 2004-2022 www.cfsph.iastate.edu page 4 of 9 Africa, these species should not be housed in the same area. Care should be taken to avoid spreading the virus on fomites. Vaccination with vaccinia virus (smallpox vaccine) is protective in nonhuman primates. Research suggests this vaccine is also protective in some other species such as prairie dogs. Anyone who has been exposed to monkeypox should avoid contact with animals that might be susceptible to infection, particularly rodents and nonhuman primates. Morbidity and Mortality A few outbreaks have been reported among captive primates, but the only cases observed in wild species were in an infant sooty mangabey found dead with pox lesions and an outbreak in a group of monitored chimpanzees in 2017-2018. Based on these reports, both published recently, and a study that found antibodies in 8% of nonhuman primates in Africa, it appears likely that some clinical cases in wild primates are missed. The morbidity rate in nonhuman primates is usually high and the mortality rate low, with most adult animals recovering. More severe illnesses may be seen in infants, which sometimes die, and primates of all ages infected experimentally via aerosols. There also seem to be speciesrelated differences in susceptibility. Crab-eating macaques (Macaca fascicularis) appear to be more susceptible than rhesus macaques (M. mulatta), and 6 of 9 captive Asian orangutans (Pongo pygmaeus) died in an outbreak at the Rotterdam zoo while two gorillas and most chimpanzees survived despite becoming ill. As of 2020, only a single clinical case has been described in a wild rodent in Africa, a squirrel (Funisciurus anerythrus) with poxvirus lesions. However, antibodies are reported regularly in African squirrels of the genera Funisciurus and Heliosciurus, and high seroprevalence rates have sometimes been found in other species, such as Natal multimammate mice (Mastomys