Updated: Dec 09, 2016
  • Author: Mary Beth Graham, MD; Chief Editor: William D James, MD  more...
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In 1970, when smallpox was nearly eradicated, a previously unrecognized orthopoxvirus named monkeypox was identified in humans. The first known human case occurred in the Equateur province of Zaire (now known as the Democratic Republic of Congo [DRC]) when a 9-year-old boy developed a smallpoxlike illness, which was eventually confirmed as human monkeypox by the World Health Organization. [1] Retrospectively, similar cases occurring in 1970-1971 from the Ivory Coast, Liberia, Nigeria, and Sierra Leone were attributed to monkeypox infection.

Monkeypox was limited to the rain forests of central and western Africa until 2003, when the first cases in the Western Hemisphere were reported. In late spring 2003, multiple persons were identified in the midwestern United States who had developed fever, rash, respiratory symptoms, and lymphadenopathy following exposure to ill pet prairie dogs (Cynomys species) infected with the monkeypox virus. [2]

Note the image below.

Vesicular rash on the dorsal aspect of the hand. V Vesicular rash on the dorsal aspect of the hand. Vesicopustules are seen; some have a central umbilication.

Most confirmed cases reported direct contact or exposure to ill prairie dogs showing signs of profuse nasal discharge, ocular discharge, dyspnea, lymphadenopathy, and mucocutaneous lesions. Traceback investigators concluded that all confirmed cases of monkeypox were associated from a common animal distributor where prairie dogs were housed or transported with African rodents from Ghana. Among these rodents were Gambian rats, which are known reservoirs of monkeypox in their native habitat of Africa.

In the 2003 US outbreak, imported asymptomatic animals transmitted a nonindigenous pathogen to an indigenous susceptible animal. After an average incubation period of 12 days, the animal became ill and was capable of transmitting the pathogen to humans when in close proximity. The potential for human-to-human transmission and human-to-animal transmission remains unknown.



The monkeypox virus is a member of the genus orthopox (family Poxviridae); other members include cowpox, vaccinia, and variola (smallpox) viruses. [3] It is a zoonotic virus with primary transmission believed to occur through direct contact with infected animals or possibly by ingestion of their inadequately cooked flesh. Inoculation may be from cutaneous or mucosal lesions on the animal, especially when the skin barrier is compromised secondary to bites, scratches, or other trauma. The infection was first seen in laboratory monkeys in 1958, thus, the name monkeypox, although rodents are believed to be the major reservoir in Africa. [4, 5] A 2010 study reaffirmed that several species of forest-dwelling rodents are at risk for orthopoxvirus (including monkeypox) infection. People living in or near the forested areas may have indirect or low-level exposure, possibly leading to subclinical infection. [6]

Secondary, or human-to-human, disease transmission was found to be another possible route in an outbreak in the DRC in 1996-1997. [5] Studies of this outbreak suggested that within households, monkeypox was secondarily transmitted to 8-15% of human contacts. Prior to this, monkeypox was not identified as an important worldwide health problem because human infection rates were not known to play a significant role in the pathogenesis. Analysis of the 2003 US outbreak implicates animal-to-animal and animal-to-human transmission as the significant route of transmission. However, in the 2003 US outbreak, clear exposure to an infected animal could not be identified in one case, and, therefore, human-to-human transmission could not be excluded.




United States

No cases occurred in the United States until the late spring 2003 outbreak in the Midwestern states. Between May 16 and June 20, 2003, 71 suspected cases of monkeypox were investigated. [7] A total of 47 individuals were identified with confirmed (n = 37) or probable (n = 10) monkeypox virus infection. Monkeypox cases were confirmed on the basis of virus isolation or detection of the virus by polymerase chain reaction (PCR) from a clinical specimen (eg, skin biopsy or throat culture). Individuals who presented with fever and rash within 21 days of exposure to monkeypox and had serum positive for orthopox immunoglobulin M (IgM), but did not have culture- or PCR-positive clinical specimens, were classified as having a probable case of infection. [8, 9]


This condition is rare and only known to be indigenous to the rain forests of western and central Africa. [10] It was first recognized in humans in 1970 after the eradication of smallpox, possibly because of the subsequent unmasking of the infection. Surveillance reports from 1981-1986 documented 338 cases in the DRC (out of a 1982 estimated population of 5 million). In the 1996-1997 outbreak in the DRC, the attack rate was 22 cases per 1000 population.

Human infection with monkeypox has not been reported in West Africa since 1978. Monkeypox is considered endemic in northern and central DRC. Sporadic occurrences of disease are reported in neighboring countries. In 2003, 11 cases and 1 death were reported from the DRC and 10 cases with no deaths were reported from Sudan in 2005. [11]

In 2009, interethnic violence in northwestern DRC lead to an influx of refugees into the Republic of the Congo (ROC). The United Nations International Children's Emergency Fund (UNICEF) sponsored a program of intensive community education in the refugee settlements that included modules on monkeypox recognition and prevention, which resulted in the indentification of 10 suspected cases of monkeypox. Seven of these 10 cases were tested and 2 were found to be positive by polymerase chain reaction assays. [12]

The results of this outreach campaign suggest that intensive community education can lead to increased capacity for detection of monkeypox in high transmission–risk settings. They also highlight the need to educate physicians in the recognition and treatment of monkeypox. [13]


Poxvirus infections have no racial predilection.


The incidence is equal in males and females.


In the African epidemics, 90% of the patients were children younger than 15 years. [14] In the recent US outbreak, of the confirmed cases in 2003 (n = 35), 11 patients were younger than 18 years and 24 were older. Although the highest age-specific incidences and the greatest number of cases occur among persons younger than 15 years, a trend toward increasing incidence among persons aged 15-30 years has been seen in recent years. It has been hypothesized that cessation of smallpox vaccination may be a factor in the increasing incidence in this age group, but this theory fails to account for why the disease has not reemerged in countries where the disease was seen previously, such as West Africa. [11]



Mortality rates ranging from 1-10% have been reported in Africa, but no fatalities occurred in the United States 2003 outbreak. Death rates are disproportionately high in African children. Health status, comorbidities, vaccination status, and severity of complications influence the prognosis in the United States and Africa.

Uncomplicated cases resolve in 2-4 weeks, with only pock scars remaining.


The disease in the United States was generally self-limited, with resolution in 2-4 weeks, depending on the severity of the illness. However, a small subset of patients, most commonly pediatric patients, had a more severe course, with several patients requiring ICU care. [15]

Complications reported from African outbreaks include pitted scars, deforming scars, secondary bacterial infection, bronchopneumonia, respiratory distress, keratitis, corneal ulceration, blindness, septicemia, and encephalitis.

Data from the African outbreaks suggest that prior smallpox vaccination confers 85% protection from monkeypox; infection may be milder even several years after vaccination, and the incidence of complications may be reduced. [16, 17] With the 2003 US outbreak, the Centers for Disease Control and Prevention (CDC) recommended smallpox vaccination up to 2 weeks, ideally within 4 days, after a significant, unprotected exposure to a diseased animal or a confirmed human case. [18]

African cases have mortality rates of 1-10%, with the highest rates occurring in children and individuals without vaccination. In general, the prognosis is related to the amount of exposure to the virus, host immune response, comorbidities, vaccination status, and severity of complications.

Genomic sequencing of US, western African, and central African monkeypox isolates have confirmed the existence of 2 distinct monkeypox clades. [19] The isolates from the United States were identical to the western African isolates. The disease course for individuals infected with the western African isolates is milder with less human-to-human transmission than for those infected with isolates from central Africa. [20] In 2010, a dosage comparison using a prairie dog animal model reconfirmed that the Congo Basin strain of monkeypox virus is more virulent than the West African strain of monkeypox virus. [21]


Patient Education

After the 2003 outbreak, the CDC implemented an immediate embargo on the importation of all rodents (order Rodentia) from Africa.

In addition, the CDC and the Food and Drug Administration prohibited the transportation or offering for transportation in interstate commerce, or the sale, offering for sale, or offering for any other type of commercial or public distribution, including release into the environment of prairie dogs and the following rodents from Africa: tree squirrels (Heliosciurus species), rope squirrels (Funisciurus species), dormice (Graphiurus species), Gambian giant pouched rats (Cricetomys species), brush-tailed porcupines (Atherurus species), and striped mice (Hybomys species).

Investigation of the exotic pet industry by state and federal authorities was triggered by the 2003 outbreak. The US Food and Drug Administration (FDA) lifted its restrictions on pet prairie dogs in 2008. The FDA consulted with the CDC and determined that the domestic restrictions placed on certain African rodents, prairie dogs, and certain other animals were no longer needed. However, the CDC restriction on the importation of all African rodents remains in effect to prevent any reintroduction of the monkeypox virus into the United States. [22]