Monkeypox virus is an orthopox virus and measures 200-250 nanometers. There are two clades (a West African and a Congolese). Morphologically it is indistinguishable from smallpox virus. The distinction can, however, be made by culture in embryonated chicken eggs and on clinical grounds. Monkeypox is pathogenic for monkeys, flying squirrels and rabbits. Monkeypox only occurs naturally in Africa, and has its reservoir in rodents. Animals such as monkeys ar anteaters are incidental hosts. The first cases that were detected date from 1958 (infections in captured monkeys). The first case in humans was recognised in 1970 in Congo. Cases have also been reported in Liberia, Nigeria, Ivory Coast, Cameroon and Sierra Leone. All the cases that have occurred involved people living in wooded environments (tropical rainforest). In monkeys, the virus causes a disease that resembles smallpox. From February 1996 to October 1997, 551 cases were reported from Congo with a case-fatality of 1.5%. Monkeypox is transmitted by direct contact (e.g. from hunting, skinning, preparing and eating infected rodents or monkeys), monkey bites or via the respiratory route. There are possibly other unknown routes of transmission. Person-to-person transmission is rare (secondary and even tertiary transmission), which greatly reduces the risk of epidemics. Only few people (mostly children) die from monkeypox. No postmortem data are available. After infection immunity is acquired and there is complete cross-protection against smallpox and vaccinia. No cases of monkeypox are known in people who have ever been vaccinated against smallpox. On the other hand, discontinuation of vaccination against smallpox has increased the number of vulnerable individuals.

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In June 2003 monkeypox arrived in the Western Hemisphere. As far as is known, this never happened before. Dozens of people in the Midwest (USA) have been sickened by the monkeypox virus after coming into contact with pet prairie dogs. Those pets became infected via an imported giant rat from Africa. Exotic pets often bring exotic health threats.

After an incubation period of 12 days (range 5-21), the patient develops fever and vague symptoms for two days. On the third day, a typical skin rash appears that develops over the course of 2 to 4 days. The skin rash is more pronounced on the face and limbs. Palms of the hand and soles of the feet also exhibit a rash. Nearly all patients have marked headache, fever and chills. About 50% will develop marked cervical and inguinal lymphadenopathy, which -in general- does not occur in smallpox. The papules become pustules and exhibit a small central indentation, like molluscum contagiosum. This is followed by crusting and after ten days the lesions heal with small scars. In milder cases, there may be fewer than 10 pustules, from which the crusts fall off after five days. The disease mostly follows a mild course and complete recovery is the rule. An important difference from smallpox is simply that smallpox has been eradicated. Lymphadenopathy is not present in smallpox and there should be no history of contact with infected animals in smallpox. Isolation of the virus and analysis of the DNA and antigens allow formal identification. Treatment is purely symptomatic. For safety sake, the patient should be isolated until the crusts fall off. The primary reservoir is unknown, but most patients will have had contact with wild-caught or killed monkeys. Varicella is the principal differential diagnosis. Certainly in AIDS patients the presentation may be very dramatic. In varicella, both early and older lesions are present simultaneously. In monkeypox the lesions are uniform.